Target cells specifically using cell-surface markers
The Society for Neuroscience meeting is just around the corner. Come visit us in Chicago – October 19-23, Booth #763.
Here are a list of the posters competing for the Annual Post of the Year Award using ATS products. (click to zoom)
Nilupaer Abudukeyoumu! Her poster was presented at the 2018 Society for Neuroscience meeting that was held in San Diego, CA:
Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons
Authors on the winning poster are pictured below L. to R.: Nilupaer Abudukeyoumu, Marianela Garcia-Munoz, Yoko Nakano, and Gordon W. Arbuthnott.
Nilupaer Abudukeyoumu is a PhD student in Dr. Arbuthnott’s laboratory in the Brain Mechanism for Behavior Unit, Okinawa Institute of Science and Technology Graduate University, Japan.
Read this article for more details about their exciting work.
Congratulations!
F055 Behavioral effects of immunotoxin 192IgG-saporin depends on the type of its administration to rats.
Yulia Dobryakova, Alexey Bolshakov, Maria Zaichenko, Mikhail Stepanichev, Vlaimir Markevich
featuring IT-01 192-IgG-SAP (Sunday 2:
It is known that degeneration of cholinergic neurons is one of key events during development of Alzheimer’s disease. We used immunotoxin 192IgG-saporin, a conjugate of antibody to p75/NFGR receptor with saporin, to induce the cholinergic deficit in the hippocampus. Here, we compared effects of intracerebroventricular (i.c.v.) and intraseptal injection of 192IgG-saporin on the learning performance in rats. Immunohistochemical analysis of the ChAT stained sections showed that both types of 192IgG-saporin injection led to a strong loss ChAT-positive neurons in septal area compared to control. Behavioral testing began 3 weeks after the injection.
We found that, in Morris Water Maze, i.c.v. injected rats had longer latencies to reach the platform and higher distance swam compared to control when the animals learned to find platform. We found that during probe trial, when the platform was removed from the maze, i.c.v.-treated rats spent significantly less time in a quadrant, where the platform was during training, and swam shorter distance in it, as compared to the control animals. Rats treated intraseptally with the immunotoxin had no behavioral deficits in the Morris Water Maze. In the beam walking test both groups of rats showed small but significant reduction of motor performance (p<0.05). In contrast, locomotor and exploratory activity in the open field task was affected only by intraseptal toxin administration as compared to the control. In conclusion, our data suggest that different types of immunotoxin administration leads to different disturbances in behavior.
The work was supported by Grant of Russian Science Foundation No 16-15-10403.
C038 Improvements in cognitive function after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis.
Jaewoo Shin, Chanho Kong, Jihyeon Lee, Young Cheol Na, Won Seok Chang, Jin Woo Chang
featuring IT-01 192-IgG-SAP (Monday 9:
Introduction: Alzheimer’s disease is irreversible and progressive neurodegenerative disorder that destroys memory and cognitive function. Recently, focused ultrasound (FUS) has been demonstrated that FUS- mediated BBB opening induces an increase in hippocampal neurogenesis in adult rodents. In this study, we investigated the effects of FUS on memory and cognitive function after 192 IgG-saporin lesioning.
Materials and Methods: The present study utilized adult male Sprague-Dawley rats (200-250 g). Animals were divided into the three groups: Sham group (PBS injection), Lesion group (saporin injection), FUS group (saporin + FUS treatment). Lesion groups were injected bilaterally into the lateral ventricle. Rats were sonicated by using a single-element transducer with microbubble. The acoustic parameters for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 24 hours after sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training.
Results: In the water maze test, the FUS groups were significantly increased in number of crossing and platform zone, compared to the lesion group. We confirmed that the number of BrdU+, DCX+, and NeuN+ were significantly increased in the dentate gyrus following FUS sonication, compared to the lesion groups.
Conclusion: Our results suggest that FUS treatments led to spatial memory improvement in cholinergic deficits rat model. These provided evidences indicate that reason of the behavior change may be induced by increase of acetylcholine activity and neuronal plasticity.
F038 Expression of NR2B subunit of the NMDA receptor and spatial long-term memory in medial septal lesioned rats.
L Kruashvili, M Dashniani, G Beselia, N Chkhikvishvili
featuring IT-32 GAT1-SAP; IT-01 192-IgG-SAP (Monday 9:
The present study was designed to investigate the effect of selective immunolesions of cholinergic and GABA- ergic SH projection neurons (using 192 IgG-saporin and GAT-1 saporin, respectively) on spatial memory assessed in water maze and the N-methyl-D-aspartate (NMDA) receptor GluN2B subunit expression in the rat hippocampus. Animals were tested in a standard Morris water maze. We found that immunolesion of medial septal cholinergic neurons did not affect spatial learning as exhibited by a decreased latency to find the hidden platform across the eight training trials. In contrast, rats with immunolesions of medial septal GABAergic neurons did not show a decreased latency across training trials in water maze. Trained control rats spent significantly longer than chance (15 s) performances such as swimming time in test sector (where the hidden platform was located). Moreover, they spent significantly longer in test sector than in the opposite sector, confirming the establishment of long-term memory. In contrast, the preference for test sector was abolished in medial septal immunolesioned rats. Because Saporin treated rats learned the location of the hidden platform during training, the results suggest that saporin treated rats could not remember the training a day later. We found that the expression level of NR2B subunit of NMDA receptor in the hippocampus was decreased significantly in the GAT-1 treated group compared with the control and saporin treated groups. In conclusion, our findings suggest that immunolesion of medial septal GABAergic neurons can interrupt hippocampus-dependent spatial learning, possibly through modulation of NMDA receptor subunit expression in the hippocampus.
F044 Effects of lesions of medial septal area on spatial short-term memory.
Khatuna Rusadze, Reniko Sakandelidze, Mariam Chighladze
featuring IT-32 GAT1-SAP; IT-01 192-IgG-SAP (Tuesday 2:
In the present study electrolytic and the immunotoxins (192 IgG saporin and GAT1-SAP) lesions of medial septal area (MS) were used to investigate the importance of cholinergic and GABAergic MS neurons in spatial working memory using spatial alternation task. In our experiments electrolytic lesions destroyed on average 69% of the intact MS. Examination of the AChE stained sections showed that after injections of 192 IgG saporin into the MS, animals exhibited significantly less AChE staining in MS as compared to sections obtained from control animals. Intraseptal GAT1-SAP preferentially reduced GABAergic neurons as compared to cholinergic neurons in the MS. The results of present study indicate that spatial short-term memory is affected only by electrolytic but not 192 IgG saporin or GAT1-SAP lesions. The behavioral testing showed that 192 IgG saporin treated rats, relative to control rats, had a significantly lower level in the number of arms entered during the testing session. However, the groups did not differ in the level of alternation behavior. GAT1-SAP lesioned rats showed that the percent alternation scores and the number of arms that the rat entered in the maze were not significantly different from control rats.
Since 2000, Advanced Targeting Systems has presented an award each year at the Society for Neuroscience meeting for the best Poster of the Year using ATS targeting tools. This year the competition was fierce and some very exciting science was presented.
Congratulations to Luiz Oliveira for winning the annual Poster of the Year award at the Society of Neuroscience meeting. Dr. Oliveira is from University of Sao Paulo in Brazil and used Orexin-B-SAP (Cat. #IT-20) in his poster:
“Role of orexinergic neurons in the chemosensory control of breathing in a Parkinson’s disease model”
The runners-up this year were:
Also, a big congratulations to the winner of the drawing for a $500 product credit: Melissa Edler from Northeast Ohio Medical University in Rootstown, Ohio USA!
72.2 /KK24 Glutamate and adenosine, basal forebrain and cortex: Cross-talk during prolonged wakefulness
A A Larin, S A Karpova, R W Mccarley, R Basheer, A V Kalinchuk
featuring IT-01 192-IgG-SAP (Poster; Saturday, Nov. 11, 1:00 PM – 5:00 PM)
Recently we described a biochemical cascade which is critical in promoting recovery sleep (RS) after sleep deprivation (SD). It is initially triggered in the basal forebrain (BF) and later in the prefrontal cortex (PFC). This cascade includes production of inducible nitric oxide synthase (iNOS)-dependent NO followed by an increase in adenosine (AD). We hypothesized that iNOS induction is triggered by an increase in extracellular glutamate (Glu), and that the increase in AD prevents further rise in Glu via its inhibitory action on AD A1 receptor (A1R). To test this hypothesis, during 8h of SD, we first examined the time course of Glu and AD in BF/PFC. Further, to investigate the role of BF Glu receptors (GluRs) in this cascade, we measured the changes in BF/PFC AD and NREMs/delta after: a) stimulating BF GluRs by NMDA or AMPA without SD; b) blocking BF GluRs during SD by NMDAR or AMPAR selective antagonists. Finally, we measured Glu in the BF/PFC after blocking A1R. Furthermore, to determine the cellular target of glutamate effects, we examined the effects BF AMPA infusion on BF/PFC AD and NREMs/delta after BF cholinergic (ChBF) lesions using 192 IgG-saporin. Male rats were implanted with EEG/EMG recording electrodes and microdialysis guide cannulae targeting the BF and PFC. Microdialysis samples were collected during 8h SD and/or drug infusion. AD and Glu were measured using high performance liquid chromatography (HPLC) and ultra HPLC. To block NMDAR/AMPAR/A1R we used dizoclipine (MK-801)/6,7- dinitroquinoxaline-2,3-dione (DNQX)/8 cyclopentyltheophylline (CPT), respectively. 1) In the BF, Glu dramatically increased at the beginning of SD, followed by increase in AD at 2 h of SD. When AD maximized at 4 h of SD, Glu concurrently decreased to baseline. High AD levels were maintained till the end of SD. In the PFC, Glu significantly increased within 2h of SD. When AD increased at 5 h of SD, Glu returned to the baseline. 2) BF AMPA mimicked the effects of SD by increasing AD in both BF and PFC. NREMs/delta increased post AMPA-infusion. NMDA was not effective. 3) BF DNQX prevented AD increase during SD in BF/PFC and attenuated RS. MK-801 did not show any effect. 4) CPT Infusion to the BF/PFC induced dramatic increase in Glu till the end of SD. 5) Lesion of ChBF prevented BF/PFC AD increase during AMPA infusion and attenuated NREMs/delta post-infusion. A rapid increase in Glu during SD may be a trigger for the induction of iNOS-NO-AD cascade in both the BF and PFC. AD via A1R exerts a negative feedback on Glu neurotransmission, preventing its further rise and potential toxicity during long-term SD. The effect of Glu on SDinduced changes is primarily mediated via AMPAR, located on ChBF cells.
201.12 / C29 Improvements in memory after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis
C Kong, J Shin,, J Lee,, C-S Koh, M-S Yoon,, Y Na, J Chang,, W Chang
featuring IT-01 192-IgG-SAP (Poster; Sunday, Nov. 12, 1:00 PM – 5:00 PM)
Abstract Introduction: Alzheimer’s disease is characterized pathologically by neurofibrillary tangles, amyloid plaques, gliosis, synaptic loss and cholinergic deficits. Recently, cell proliferation and neurogenesis was reported to have increased when the blood brain barrier (BBB) was disrupted by Focused ultrasound (FUS) with microbubbles. Previously, we have demonstrated that the cholinergic cell decreases in 192 IgG-saporin rat model, and that decrease in cholinergic cell is associated to decrease in cognitive behavior. The purpose of this study was to determine if the learning and memory abilities of the 192 IgG-saporin rat model are improved by FUS. Materials and Methods: Animals were divided into the four groups: Sham group (PBS injection), Lesion group (saporin injection), FUS-3 and FUS-10 groups (After 3 and 10 days after saporin injection, FUS treatment). Sprague-Dawley rats (200-250g) were injected bilaterally with 192 IgG-saporin into the ventricle. Rats were sonicated using a single-element transducer (frequency 0.5 MHz) with microbubble. The acoustic parameters used for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. To confirm cell proliferation, BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 24 hours after FUS sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training for 5 days and the final test was performed. Results: In the water maze test, the FUS groups had a higher number of crossing times and staying time in the platform zone than the lesion group. Also, the FUS-3 group was higher than for the FUS-10 group. We confirmed that the amounts of DCX , NeuN , and BrdU were different between the FUS group and the lesion group. Conclusion: Our results suggest that FUS sonication facilitates recovery of memory and learning abilities in cholinergic deficits rat model. Moreover, the results suggest that neurogenesis is correlated with the mechanism of cognitive behavior recovery.
233.1 / FF22 Local glutamatergic transmission in the RTN/pFRG is critical for active expiration and sympathetic overactivity during hypercapnia
W H Barnett, Y I Molkov, E Lemes, B Falqueto, E Colombari, A T Takakura, T S Moreira, D B Zoccal
featuring IT-11 SSP-SAP (Poster; Sunday, Nov. 12, 1:00 PM – 5:00 PM)
The retrotrapezoid nucleus (RTN) contains chemosensitive cells that distribute CO -dependent excitatory drive to the brainstem respiratory network. This drive facilitates the function of the respiratory central pattern generator (CPG), modulates sympathetic activity and determines the emergence of active expiration during hypercapnia via activation of the late expiratory (late-E) oscillator in the parafacial respiratory group (pFRG). However, the microcircuitry responsible for distribution of the chemoreflex signal to the pFRG and the respiratory CPG is not well understood. Previously, we developed a computational model of the brainstem respiratory network, which was subsequently extended to include the central and peripheral chemoreflexes as well as presympathetic circuits. We present here experiments performed on the decerebrated, arterially-perfused in situ rat, aimed to test a key assumption of this model that chemosensitive and late-E neurons in the RTN/pFRG are two distinct populations, and the latter receives local glutamatergic input from the former. The model predicts: (1) suppression of RTN chemosensitive neurons will diminish the changes to the respiratory pattern and the emergence of active expiration associated with hypercapnia; (2) the disruption of local glutamatergic neurotransmission in the RTN will specifically suppress active expiration and the appearance of late-E discharges in the sympathetic motor output. To test prediction (1) we lesioned NK1 -positive chemosensitive neurons of the RTN with microinjections of substance P-saporin (SSP-SAP) conjugate. This suppressed the emergence of late-E activity in abdominal (AbN) and sympathetic nerves, and attenuated the increase in phrenic burst amplitude during hypercapnia. However, SSP-SAP and control animals exhibited late-E AbN activity in response to peripheral chemoreflex activation. Prediction (2) was tested with bilateral microinjections of kynurenic acid (Kyn, 100 mM) in the RTN/pFRG, which suppressed the emergence of late-E AbN activity but not the change in phrenic nerve amplitude during hypercapnia. Our results support the notion that RTN chemosensitive neurons are critical for inspiratory and expiratory reflex responses to hypercapnia. Our findings indicate that activation of late-E neurons in the pFRG during hypercapnia requires glutamatergic inputs from a separate neuronal population in the RTN that intrinsically detects changes in CO . During peripheral chemoreflex stimulation, pFRG late-E neurons are activated via excitatory pathways bypassing the RTN central chemoreceptors. We recapitulate these results in our computational model.
237.03 / HH34 Behavioral effects following ablation of retinalganglion cells in diurnal grass rats
G Fogo, A J Gall
featuring IT-44 Melanopsin-SAP (Poster; Sunday, Nov. 12, 1:00 PM – 5:00 PM)
Light influences behavior and physiology in mammals by entraining circadian rhythms and also through direct and acute inhibition or stimulation of activity, a process called masking. Although there has been substantial progress elucidating the mechanisms responsible for the workings of the circadian system in nocturnal species, less is known about the mechanisms that support the diurnal profile of activity of mammals, especially as they relate to the retina. We recently showed that the intergeniculate leaflet (IGL) is critical for the display of normal patterns of daily activity in diurnal grass rats (Arvicanthis niloticus). Specifically, IGL lesions reverse the activity patterns of these animals such that they became night-active; this occurred through their effects on both circadian mechanisms and masking. The IGL is a thalamic structure that receives direct inputs from the melanopsin containing intrinsically photosensitive retinal ganglion cells, known as ipRGCs. Our current approach takes advantage of a diurnal mammalian model, the Nile grass rat, to test the novel hypothesis that melanopsin is critical for the expression of diurnal behavior and physiology, and is involved in masking responses to light. We will achieve this goal by injecting the immunotoxin anti-melanopsin-saporin intraocularly in grass rats and examining behavior following this experimental manipulation. Animals will be placed in various lighting conditions, including 12:12 light-dark conditions, and will be given pulses of light to test for effects of masking. We predict that controls will exhibit more general activity during the day, consistent with a diurnal species, and will exhibit increased activity following acute pulses of light. We predict that animals with the melanopsin toxin in the retina will be out of phase with controls in behavior following acute pulses of light, similar to animals with IGL lesions. Altogether, we are building a model to understand the mechanisms underlying the normal display of diurnal behavior, and we hope to add to this knowledge by examining how melanopsin contributes to the display of diurnal behavior in grass rats.
241.1 / LL2 Basal forebrain cholinergic neurons are vital for cortical desynchronization and behavioral arousal observed after nicotine consumption
A Sharma, R Sharma, C Mackey, P Sahota, M Thakkar
featuring IT-01 192-IgG-SAP (Poster; Sunday, Nov. 12, 1:00 PM – 5:00 PM)
Purpose: Nicotine is an addictive constituent of tobacco which severely affects behavior. Sleep disruptions including reducing total sleep time, increasing sleep fragmentation and reducing sleep efficiency are very common in nicotine users. However, the underlying neuronal mechanism of how nicotine promotes desynchronization and disrupts sleep is unknown. We have shown that the basal forebrain (BF) is a key brain region, mediating nicotine’s effects on sleep-wakefulness (SFN 2015; Poster#166). The BF contains multiple neuronal phenotypes including cholinergic, GABAergic and glutamatergic subtypes. Thus, this study was designed to examine the neuronal subtype responsible for nicotine effects on sleep-wakefulness. As a first step, we focused on BF cholinergic neurons because BF cholinergic neurons are wake-promoting, express nicotinic receptors and supply acetylcholine to the prefrontal cortex, hippocampus and amygdala. We hypothesized that lesions of BF cholinergic neurons will attenuate nicotine induced cortical arousal/desynchronization. Methods: To test our hypothesis, adult male Sprague-Dawley rats were implanted with sleep recording electrodes and were divided into two groups: Lesion: Selective lesion of the BF cholinergic neurons was performed by bilateral administration of immunotoxin, 192-IgG-Saporin (SAP; 0.28 µg/0.5µL/side) in the BF; Sham (controls): Rats were bilaterally infused with saline (0.5µL/side). After injections, animals were left undisturbed for 3 weeks. Day 1: saline was administered subcutaneously at light/sleep onset. Day 2: Nicotine (0.3 mg/Kg) was administered at the same time. Sleep- wakefulness was examined for next 6 hours. On completion, animals were euthanized and the brains were processed for choline acetyltransferase (ChAT) immunohistochemistry to verify BF cholinergic lesions. Results: Our preliminary results: As compared to controls, lesioned rats, with a 64% reduction in cholinergic neurons, displayed attenuated nicotine induced cortical desynchronization and behavioral arousal. Conclusions: Our results suggest that the BF cholinergic neurons mediate nicotine induced cortical arousal/desynchronization that may be the cause of sleep disruptions in nicotine users.
244.02 / NN6 Chemogenetic activation of a retinal circuit that activates locus coeruleus neurons prevents the development of light- deprivation induced depression-like behavior
H E Bowrey, M H James, A Mohammadkhani, M Omrani, G Kane, G Aston-Jones
featuring IT-44 Melanopsin-SAP (Poster; Sunday, Nov. 12, 1:00 PM – 5:00 PM)
Introduction: Chronic light-deprivation induces a depressive-like phenotype via a locus coeruleus norepinephrine (LC-NE)- dependent mechanism (Gonzalez and Aston-Jones, 2008). Suprachiasmatic nucleus (SCN) provides indirect circadian input onto LC via dorsomedial hypothalamus (DMH) (Aston-Jones et al 2001). SCN is therefore in a key position to integrate light information with LC via the pathway: retina→SCN→DMH→LC. We refer to this pathway as the Photic Regulation of Arousal and Mood (PRAM) pathway. We tested the hypothesis that increasing PRAM pathway activity prevents darkness-induced depression-like behavior.
Methods: Expt 1. Sprague Dawley rats received intraocular injections of excitatory hM3Dq DREADD (AAV2-hSyn-hM3D(Gq)- mCherry) control virus (AAV2-hSyn-EGFP) or no virus. Rats were placed in continuous darkness for 8 weeks, and those that received virus were concurrently subjected to daily intraperitoneal injections of clozapine-N-oxide (CNO; 2 mg/kg), the DREADD-activating ligand. Rats were then subjected to assays of mood (saccharin preference test, elevated plus maze and forced swim test) or vision (electroretinagram: ERG). LC tissue was stained for Poly ADP ribose polymerase (PARP, a marker of apoptosis) and tyrosine hydroxilase (TH). Expt 2. To determine the retinal cell-type responsible for depression-like behavior, intrinsically photosensitive retinal ganglion cells (ipRGCs) of animals raised in 12:12 light:dark conditions were ablated using a saporin (SAP) toxin that selectively eliminates melanopsin-expressing cells (Mel-SAP). Two control groups received intraocular injections of vehicle and were kept in either continuous darkness or in 12:12 light:dark conditions. Ten weeks later, rats were subjected to identical analyses as those in Expt 1. Results: Expt 1. ERG analysis showed that CNO-activation of retinal DREADDs increased RGC activity. Constant darkness induced a depression-like phenotype in control animals, which was prevented by daily activation of retinal DREADDs by CNO. Expt 2. Mel-SAP induced a depression-like phenotype in animals maintained in normal light-dark conditions. This was also associated with increased apoptosis in LC-NE cells as seen with PARP staining. Conclusion: Dysregulation of the PRAM pathway may induce neural damage in LC-NE neurons that is associated with a depressive behavioral phenotype. DREADD-induced activation of RGCs can prevent depression-like behaviors that normally occur in rats kept in chronic darkness. The PRAM pathway presents a novel circuit for the regulation of mood, and thus a possible new direction for the treatment of some forms of depression in humans.
317.06 / HH5 Vagus nerve stimulation dependent enhancement of motor cortex plasticity requires noradrenergic innervation
D Hulsey, M Shedd, J Mong, R L Rennaker, S A Hays, M P Kilgard
featuring IT-03 Anti-DBH-SAP (Poster; Monday, Nov. 13, 8:00 AM – 12:00 PM)
Pairing forelimb movements with vagus nerve stimulation (VNS) drives robust plasticity within primary motor cortex (M1). VNS activates cholinergic circuits, which are required for VNS-depended enhancement of plasticity. However, there may be multiple neuromodulatory mechanisms required for VNS-dependent enhancement of plasticity. Norepinephrine regulates plasticity, and the noradrenergic locus coeruleus is driven vigorously by VNS. However, the role of norepinephrine in VNS-dependent enhancement of plasticity is unknown. We hypothesize that noradrenergic innervation of M1 and/or basal forebrain is necessary for M1 plasticity associated with VNS pairing. To test this, we trained rats on a skilled lever press task emphasizing use of the proximal forelimb.
After demonstrating proficiency on the task, rats received M1 injections of vehicle or DBH-Saporin to selectively deplete norepinephrine in motor cortex, and underwent implantation of a stimulating cuff electrode on the vagus nerve. Sham and NE- lesioned rats resumed training one week after surgery. After returning to pre-surgical performance, both groups received 10 sessions of training with VNS paired on successful trials. Intracortical microstimulation was performed to derive M1 maps within 24 hours of the final training session. Initial data suggests that sham lesioned animals who receive VNS pairing with successful trials show a robust expansion of proximal forelimb movements represented in M1. Noradrenergic lesion of M1 blocks this VNS- dependent expansion of proximal forelimb representation, indicating that cortical norepinephrine innervation is necessary for VNS driven plasticity. Ongoing experiments will determine whether noradrenergic input to the central cholinergic systems is required for VNS-dependent enhancement of plasticity.
414.02 / PP19 Increased core temperature following ablation of neurokinin 3 receptor-expressing neurons in the mouse median preoptic nucleus and adjacent preoptic area (MnPO/POA)
S J Krajewski-Hall, 87, E M Blackmore, J R Mcminn, N T Mcmullen, N E Rance,,
featuring IT-63 NK3-SAP (Poster; Monday, Nov. 13, 1:00 PM – 5:00 PM)
We have previously proposed that KNDy neurons play a role in the generation of hot flushes via neurokinin 3 receptor (NK3R) signaling in the preoptic hypothalamus. This hypothesis is strongly supported by recent clinical studies showing that the number and severity of hot flushes is reduced by treatment with NK3R antagonists. To determine if preoptic NK3R neurons modulate thermoregulation in the mouse, we selectively ablated them using injections of saporin conjugated to a NK3R agonist (NK3-SAP).
NK3-SAP was stereotaxically injected into Tacr3-EGFP mice to target the MnPO/POA. Controls received injections of BLANK-SAP. The mice were ovariectomized (OVX) and a telemetry probe was implanted i.p. to measure core temperature (TCORE) and activity. Skin temperature (TSKIN) was monitored using a temperature data-logger attached to the surface of the tail. In experiment 1, circadian temperature rhythms were monitored over a 3 day period in mice housed in their home cages (12 light:12 dark). In experiment 2, mice were exposed to three temperatures, 18, 28 and 35oC, in an environmental chamber. Mice were then implanted s.c. with estradiol (E2) capsules and the experiments repeated. We verified by immunohistochemistry and quantitative microscopy that approximately 80% of the EGFP-NK3R neurons in the MnPO were ablated using NK3-SAP. Ablation of NK3R neurons significantly elevated TCORE during the light phase in both OVX and OVX + E2 mice (OVX: BLANK-SAP, 36.7 + 0.1 vs NK3-SAP 37.4 + 0.1; OVX+E2: Blank-SAP 36.1 + 0.1 vs NK3-SAP 36.8 + 0.1). NK3-SAP injections had no significant effect on TCORE during the dark phase. Ablation of NK3R neurons also increased TCORE during the light phase in mice exposed to 18oC and 28oC. All mice exhibited hyperthermia at 35oC. In contrast, ablation of NK3R neurons in the MnPO/POA had no effect on TSKIN or activity regardless of experimental treatment. These data suggest that NK3R neurons in the MnPO/POA participate in the thermoregulatory axis by promoting heat loss during the day and provide further insight into the CNS thermoregulatory pathways that may be activated during the generation of hot flushes.
423.01 / TT12 Serotoninergic projections to the OFC and BLA modulate reversal learning
D Tapp, M Mcmurray
featuring IT-23 Anti-SERT-SAP (Poster; Monday, Nov. 13, 1:00 PM – 5:00 PM)
Behavioral flexibility, the ability to adapt to changing reward contingencies, is a critical aspect of choice behavior. Such ability is disrupted in numerous psychiatric disorders, such as substance abuse disorders, attention deficit disorder, and obsessive- compulsive disorder. The orbitofrontal cortex (OFC) and the basolateral amygdala (BLA) have been implicated as key regulators for this behavior. Additionally, the neurotransmitter serotonin is known to influence behavioral flexibility, and is disrupted in numerous psychiatric disorders. While serotonin and these brain regions have been examined separately, they have yet to be directly linked in this behavioral context. Using a rat model, this study examined such a relationship by selectively leisoning serotoninergic projections to the OFC, BLA, or both regions with a SERT-conjugated Saporin, and assessing behavioral flexibility in a probabilistic spatial reversal-learning task. Preliminary results indicated that the loss of serotonergic projections to either the OFC, BLA, or both impaired behavioral flexibility. Based on these results, we determined that serotonin regulates reversal learning through its action in the OFC and BLA. Therefore, the serotonergic system may serve as a future therapeutic target for diseases in which behavioral flexibility is impaired, and may explain the effectiveness of serotonin modulators in the treatment of these diseases.
428.01 / UU39 Modulation of GluN2B subunit-containing NMDA receptors expression and spatial long-term memory in medial septal immunolesioned rats
G Beselia, M Dashniani, M Burjanadze, R Solomonia, L Kruashvili, N Chkhikvishvili
featuring IT-01 192-IgG-SAP; IT-32 GAT1-SAP (Poster; Monday, Nov. 13, 1:00 PM – 5:00 PM)
The hippocampus is important in the formation of spatial memory in both humans and animals. The N-methyl-D-aspartate (NMDA) type of glutamate receptors in the hippocampus has been reported to be essential for spatial learning and memory as well as for the induction of synaptic plasticity. Evidence accumulated from recent studies suggest that GluN2A and GluN2B subunit-containing NMDA-Rs preferentially contribute to the induction of hippocampal LTP and LTD. Using a Morris water maze (MWM) task, the LTP- blocking GluN2A antagonist had no significant effect on any aspect of performance, whereas the LTD-blocking GluN2B antagonist impaired spatial memory consolidation.1The present study was designed to investigate the effect of selective immunolesions of cholinergic and GABA-ergic1septohippocampal projection neurons [using 192 IgG-saporin (SAP) or GAT1-1 saporin (GAT), respectively] on spatial memory assessed in MWM and NMDA receptor GluN2B subunit expression in the rat hippocampus. We used MWM training protocol with eight training trials. One day after training, probe test with the platform removed was performed to examine long-term spatial memory retrieval. We found that immunolesions of medial septal cholinergic or GABAergic neurons did not affect spatial learning as exhibited by a decreased latency to find the hidden platform across the eight training trials. Trained control and SAP treated rats spent significantly longer than chance (15 s) performances such as swimming time in test sector (where the hidden platform was1located). Moreover, they spent significantly longer in test sector than the opposite sector, confirming the establishment of long-1term memory. In contrast, the preference for test sector was abolished in medial septal GAT treated rats. Because GAT treated rats learned the location of the hidden platform during training, the result suggest that GAT level of NR2B subunit of NMDA receptor in the hippocampus was decreased significantly in the GAT treated group compared with the control and SAP treated groups.1In conclusion, our findings suggest that immunolesion of medial septal GABAergic neurons can interrupt hippocampus dependent1spatial memory, possible through modulation of NMDA receptor subunit expression in the hippocampus. Moreover, our finding that selective lesions of medial septal GABAergic neurons affect probe-test performance but not spatial learning, suggests that septohippocampal GABAergic projections are involved specifically in the consolidation or retrieval, but not in the acquisition of long- term memory.
507.13 / NN21 RVLM C1 neuron ablation normalizes cardiorespiratory control in heart failure
R Del Rio, D C Andrade, C Toledo, H S Diaz
featuring IT-03 Anti-DBH-SAP (Poster; Tuesday, Nov. 14, 8:00 AM – 12:00 PM)
Heart failure (CHF) is characterized by sympathoexcitation and breathing disorders. The rostral ventrolateral medulla (RVLM) is hyperactive in CHF. However, there is no direct evidence between the relationship of RVLM chronic hyperactivation, sympathoexcitation and progression of cardiac deterioration in CHF. We hypothesized that selective elimination of cathecolaminergic neurons from the RVLM delays cardiac deterioration in CHF rats. CHF was induced by volume overload in male Sprague-Dawley rats (250±20g). Ablation of C1 cells was performed by anti-dopamine-beta hydroxylase (DβH)–saporin toxin (DβH+SAP) injected into the RVLM. The degree of HF was estimated by echocardiography. Cardiac function was assessed by intraventricular PV loops. Arrhythmia index and breathing disorders were scored. Central and peripheral chemoreflex and cardiac autonomic control were also study. Partial elimination of C1 RVLM neurons (≈50%) delay the decrease in fractional shortening in CHF rats (CHF+Veh: 59±5 vs. 45±1 %, p<0.05, pre vs. post vehicle, respectively; CHF+DβH-SAP: 57±4 vs. 51±4 %, p>0.05, pre vs. post toxin, respectively). In addition, compared to CHF vehicle treated rats, CHF+DβH-SAP rats showed (CHF+Veh vs. CHF+DβH-SAP, respectively): i) a reduced cardiac sympathetic drive (-98±12 vs. -52±7 ΔHR, p<0.05), ii) an improvement in both cardiac diastolic (0.009±0.001 vs. 0.004±0.001 mmHg/µl, p<0.05) and systolic function (0.2±0.01 vs. 0.5±0.1 mmHg/µl, p<0.05), iii) a reduced number of arrhythmias (95±20 vs. 48±14 events/hour, p<0.05), and iv) a reduced incidence of breathing disorders (9±1 vs. 6±1 apneas/hour, p<0.05). Finally, the detrimental autonomic and cardiovascular effects induced by central chemoreceptors activation were abolished after C1 neurons ablation in CHF rats. Neither hypoxic nor hypercapnic ventilatory chemoreflex responses were affected by DβH- SAP treatment. Our results showed that the RVLM play a pivotal role on the progression of cardiac deterioration and in the maintenance of autonomic imbalance and breathing disorders in CHF. In addition, our results showed that the sympathoexcitation and cardiac function deterioration induced by central chemoreflex activation is related to the activation of RVLM C1 neurons.
510.22 / PP13 Gastrointestinal vagal afferent signaling promotes hippocampal-dependent memory function in rats
A N Suarez, T M Hsu, G De Lartigue, S E Kanoski
featuring IT-31 CCK-SAP (Poster; Tuesday, Nov. 14, 8:00 AM – 12:00 PM)
The vagus nerve is the primary conduit of communication between feeding-relevant gastrointestinal (GI) signals and the brain. Vagally-mediated GI satiation signals, including gastric distension and intra-gastric nutrient infusion, activate neurons in the hippocampus (HPC) through unidentified polysynaptic pathways. The functional relevance of GI-derived communication to the HPC is unknown. Here we first explored whether chronic disruption of gut-to-brain vagal tone via subdiaphragmatic vagotomy (SDV) negatively impacts HPC-dependent memory function in rats. While SDV did not impair HPC-dependent appetitive learning based on interoceptive energy status cues or social food-related cues, SDV did impair spatial working memory (Barnes maze) and contextual episodic memory (novel object in context; NOIC), two HPC-dependent tasks that involve processing of visuospatial stimuli. Next, to determine whether vagal sensory/afferent vs. motor/efferent signaling regulates HPC-dependent memory function, we employed a novel approach in which a saporin conjugated to cholecystokinin (CCK-SAP) or an unconjugated control saporin is injected into the nodose ganglia, a strategy that preserves 100% of vagal efferent signaling while eliminating ~80% of GI-derived vagal afferent signaling. Similar to SDV rats, CCK-SAP rats were impaired in both the Barne’s maze task and NOIC learning relative to controls.
Consistent with the memory deficits, immunoblot protein analyses in hippocampus lysates revealed reduced neurotophic [brain- derived neurotrophic factor (BDNF)], and neurogenesis [doublecortin (DCX)] markers in both SDV and CCK-SAP rats relative to controls. These findings indicate that GI-derived vagal afferent signaling is critical in regulating HPC-dependent mnemonic function. Results have direct clinical relevance, as procedures that chronically disrupt vagus nerve signaling (e.g., vBloc) have recently been FDA-approved for obesity treatment.
689.16 / II23 Patch compartment lesions reduce habitual sucrose consumption
K A Horner, J B Logue, T A Jenrette
featuring IT-12 Dermorphin-SAP (Poster; Wednesday, Nov. 15, 8:00 AM – 12:00 PM)
The striatum mediates habit formation and reward association. The striatum can be divided into the patch and matrix compartment, which are two neurochemically and anatomically distinct regions that may sub-serve different aspects of behavior. For example, the patch compartment may mediate reward-related behaviors, while the matrix compartment may mediate adaptive motor functions. Furthermore, previous studies have shown that enhanced relative activation of the patch versus matrix compartment is associated with inflexible behaviors, such as stereotypy. Habitual behaviors are also inflexible in nature, but whether enhanced activation of the patch compartment contributes to habitual behavior is not known. The goal of the current study was to examine the role of patch compartment neurons in the development of habit formation. We used dermorphin-saporin to specifically ablate neurons of the patch compartment prior to training animals to self-administer sucrose on a random interval schedule of reinforcement, which has been shown to foster habit formation. Our data showed that destruction of the neurons of the patch compartment prevented the reinstatement of sucrose self-administration after sucrose devaluation, indicating that absence of the patch compartment interrupted the development of habitual behavior. Our data also indicate that c-Fos levels were decreased in the dorsolateral striatum (DLS) and sensorimotor cortex (SMC), but increased in dorsomedial striatum (DMS) and prefrontal cortex (PFC) in patch-lesioned animals that did not develop habitual behavior, indicating that diminished habit formation is associated with decreased activation of regions that participate in habitual behavior, and increased in regions associated with goal-directed behaviors. Together, these data indicate that the patch compartment participates in habit formation by altering the flow of information through basal ganglia circuits.
779.08 / HH1 Role of orexinergic neurons in the chemosensory control of breathing in a Parkinson’s disease model
B Falquetto, L M Oliveira, T S Moreira, A C Takakura
featuring IT-20 Orexin-SAP (Poster; Wednesday, Nov. 15, 1:00 PM – 5:00 PM)
Parkinson´s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). Non-motor symptoms such as neuropsychiatric, sleep and breathing disorders are also observed in PD. Previous study has already demonstrated that in 6-hydroxydopamine (6-OHDA)-model of PD there is a reduction in the number of phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia. Here, we tested the involvement of orexin cells from lateral hypothalamus/perifornical area (LH/PeF) on breathing in this model of PD. 6-OHDA (24 µg/µl) injections into the striatum reduced the number of catecholaminergic (40 days: 128 ± 10 and 60 days: 116 ± 13 vs. vehicle: 938 ± 15 neurons) and orexin-B-ir neurons (40 days: 310 ± 9 and 60 days: 258 ± 15 vs. vehicle: 412 ± 13 neurons).
The injection of anti-Orexin-B saporin into the LH/PeF produces a further reduction in the number of orexinergic neurons in PD animals (79 ± 8 vs. control: 427 ± 14 neurons). The respiratory frequency (fR) at rest and in response to hypercapnia (7% CO2) was assessed 60 days after bilateral 6-OHDA or vehicle injections into the striatum and anti-Orexin-B saporin or IgG saporin into the LH/PeF during sleep and wakefulness in the dark and light phases of the diurnal cycle. Sixty days after 6-OHDA, we observed a reduction of fR at rest during sleep in the light phase only in PD animals (56 ± 2 vs. control: 66 ± 2 bpm). During the dark phase, there is a reduction in fR response to hypercapnia in PD animals with depletion of orexinergic neurons during wakefulness (119 ± 6 vs. control: 152 ± 3 bpm) and sleep (128 ± 7 vs. control: 147 ± 5 bpm). Our data suggest that orexinergic neurons are important to restore chemoreceptor function in a rat model of PD during sleep and wakefulness in rats.
38.10 / G29 Placenta-derived mesenchymal stem cells facilitate neural and cognitive recovery in dementia rat model.
featuring IT-01 192-IgG-SAP (Poster; Saturday, Nov. 12, 1:00 PM – 5:00 PM)
77.09 / AAA24 Diacylglycerol lipase-α expression increases in the coeruleo-cortical pathway in dopamine-β-hydroxylase knockout mice as well as rats treated with DSP-4
featuring IT-03 Anti-DBH-SAP (Poster; Saturday, Nov. 12, 1:00 PM – 5:00 PM)
124.06 / E30 Targeting vesicular gaba transporter (vGAT)-expressing cells with a polyclonal antibody to the lumenal domain of vGAT: results with a saporin conjugate.
featuring AB-N44 Anti-vGAT; IT-71 Anti-vGAT-SAP (Poster; Sunday, Nov. 13, 8:00 AM – 12:00 PM)
74.23 / GGG14 A unique subdivision of serotonergic neurons in the dorsal raphe nucleus projects to the basolateral amygdala complex to enhance fear-conditioned behaviors.
featuring IT-23 Anti-SERT-SAP (Poster; Sunday, Nov. 13, 8:00 AM – 12:00 PM)
245.09 / RR4 Striatal cholinergic interneurons: their depletion and its progression.
featuring IT-42 Anti-ChAT-SAP (Poster; Sunday, Nov. 13, 1:00 PM – 5:00 PM)
254.12 / AAA18 Basal forebrain cholinergic neurons are vital for sleepiness observed after alcohol consumption.
featuring IT-01 192-IgG-SAP (Poster; Sunday, Nov. 13, 1:00 PM – 5:00 PM)
256.21 / CCC20 Catecholaminergic innervation and the neuronal activation of hypothalamic glucose sensitive regions during rapid- and slow-onset hypoglycemia in adult male rats..
featuring IT-03 Anti-DBH-SAP (Poster; Sunday, Nov. 13, 1:00 PM – 5:00 PM)
257.08 / DDD9 Tectal CRF R1 receptors modulate food intake.
featuring IT-13 CRF-SAP (Poster; Sunday, Nov. 13, 1:00 PM – 5:00 PM)
262.11 / III7 The role of cholinergic input from the medial septum in cued and contextual fear extinction memory.
featuring IT-01 192-IgG-SAP (Poster; Sunday, Nov. 13, 1:00 PM – 5:00 PM)
338.01 / SS14 Maternal aggression is impaired by prepartum serotonin-specific lesions of the midbrain dorsal raphe.
featuring IT-23 Anti-SERT-SAP (Poster; Monday, Nov. 14, 8:00 AM – 12:00 PM)
525.15 / SS2 Cerebral cholinergic mechanisms in pain: CBF lesions vs systemic scopolamine.
featuring IT-01 192-IgG-SAP (Poster; Tuesday, Nov. 15, 8:00 AM – 12:00 PM)
786.11 / H7 The locus coeruleus: a potential link between cerebrovascular and neuronal pathology in Alzheimer’s disease.
featuring IT-03 Anti-DBH-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
807.20 / HH11 Enhanced motor recovery by vagus nerve stimulation requires cholinergic innervation in a rat model of ischemic stroke.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
812.14 / OO13 Novel targets for modulation of plasticity in a mouse model of motoneuron degeneration.
featuring IT-14 CTB-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
833.03 / HHH22 Effects of protein kinase C activation on attention deficits following loss of corticopetal cholinergic neurons.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
833.11 / HHH30 Cholinergic-dependent shifts to cue-directed behavior.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
833.15 / HHH34 Effects of N-desmethylclozapine on attentional performance following loss of basal forebrain corticopetal cholinergic inputs.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
835.15 / III34 Preventing falls in PD in a rat model of impaired cognitive control of complex movements by a pro-cholinergic combination treatment.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
845.01 / LLL41 Developmental disturbances in thalamocortical connection are sufficient to produce almost all features of schizophrenia.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, Nov. 16, 1:00 PM – 5:00 PM)
40.29/C34 Preliminary investigation on the antidepressive effect of chronic oxotremorine treatment in a rodent model of Alzheimer’s disease
featuring IT-01 192-IgG-SAP (Poster; Saturday, Oct. 17, 1:00 PM – 5:00 PM)
6.07 Modeling Tourette syndrome pathophysiology through targeted manipulation of striatal interneurons
featuring IT-42 Anti-ChAT-SAP (Minisymposium; Saturday, Oct. 17, 3:15 PM – 3:35 PM)
247.17/R3 Postpartum lesions targeting serotonergic neurons in the dorsal raphe alter various aspects of maternal behavior
featuring IT-23 Anti-SERT-SAP (Poster; Sunday, Oct. 18, 1:00 PM – 2:00 PM)
217.06/C66 Direct impact of dopaminergic and noradrenergic systems on adult-hippocampal neurogenesis in adult rats and the relevance to dementia in Parkinson’s disease
featuring IT-03 Anti-DBH-SAP (Poster; Sunday, Oct. 18, 2:00 PM – 3:00 PM)
253.11/V29 Cholinergic contributions to PASA and functional compensation in rats
featuring IT-01 192-IgG-SAP (Poster; Sunday, Oct. 18, 3:00 PM – 4:00 PM)
297.15/B100 Astrocytic lesions that spare neurons in the nucleus tractus solitarii interfere with cardiorespiratory control
featuring IT-03 Anti-DBH-SAP (Poster; Monday, Oct. 19, 10:00 AM – 11:00 AM)
391.10/C34 Compensatory cortical sprouting across the lifespan of the rat
featuring IT-01 192-IgG-SAP (Poster; Monday, Oct. 19, 2:00 PM – 3:00 PM)
411.15/L-15 Basal forebrain cholinergic lesions attenuate the reinstatement of cocaine-seeking produced by a discriminative stimulus in goal-trackers but not sign-trackers
featuring IT-01 192-IgG-SAP (Poster; Monday, Oct. 19, 3:00 PM – 4:00 PM)
418.11/O12 Nociceptive effects of neurotensin(NTS)- and somatostatin(SST)-toxin conjugates applied to the lumbar dorsal horn in rats
featuring Neurotensin-CTA;Neurotensin-SAP;Somatostatin-SAP; Blank-SAP (Poster; Monday, Oct. 19, 3:00 PM – 4:00 PM)
432.16/X11 Control of sympathetic activity by A5 noradrenergic neurons in the in situ rat preparations
featuring IT-03 Anti-DBH-SAP IT-18 Mouse IgG-SAP (Poster; Monday, Oct. 19, 4:00 PM – 5:00 PM)
506.23/M12 Ablation of the patch compartment reduces cocaine-induced stereotypy
featuring IT-12 Dermorphin-SAP (Poster; Tuesday, Oct. 20, 10:00 AM – 11:00 AM)
613.05/R20 Immunolesions of melanopsin receptive neurons attenuates the hormonal reproductive axis in the adult but has no effect on growth in immature Peking ducks
featuring IT-44 Melanopsin-SAP; PR-01 Saporin (Poster; Tuesday, Oct. 20, 1:00 PM – 2:00 PM)
613.04/R19 Lack of effects on growth and body weight gain after elimination of the leptin receptor from the brain of immature Pekin drakes
featuring Custom Anti-Leptin-SAP PR-01 Saporin (Poster; Tuesday, Oct. 20, 4:00 PM – 5:00 PM)
626.12/AA3 Neuroprotective effects of placenta-derived mesenchymal stem cell for rat model of dementia
featuring IT-01 192-IgG-SAP (Poster; Tuesday, Oct. 20, 4:00 PM – 5:00 PM)
676.26/D33 Cognitive and motor deficits in a rodent model of Parkinson’s disease displaying concurrent dopamine and acetylcholine loss
featuring IT-01 192-IgG-SAP IT-42 Anti-ChAT-SAP PR-01 Saporin (Poster; Wednesday, Oct. 21, 9:00 AM – 10:00 AM)
689.18/K11 Neuroprotection with androgens following partial motoneuron depletion: A role for microglia
featuring IT-14 CTB-SAP (Poster; Wednesday, Oct. 21, 9:00 AM – 10:00 AM)
694.14/N4 Selective ablation of the intercalated neurons of the amygdala increased the anxiety-like behavior in the Elevated Plus Maze
featuring IT-12 Dermorphin-SAP (Poster; Wednesday, Oct. 21, 9:00 AM – 10:00 AM)
718.10/Y20 A2 noradrenergic neurons regulate forced swim test immobility
featuring IT-03 Anti-DBH-SAP (Poster; Wednesday, Oct. 21, 9:00 AM – 10:00 AM)
692.21 Impairments in gait, posture and complex movement control in rats modeling the multi-system, cholinergic-dopaminergic losses in PD
K Phillips, A Kucinski, R Albin, M Sarter
featuring IT-42 Anti-ChAT-SAP (poster; Wednesday, Nov. 19, 8:00 AM – 12:00 PM)
In addition to striatal dopamine loss, degeneration of cholinergic neurons in the basal forebrain (BF) and the brainstem pedunculopontine nucleus (PPN) were documented in patients with Parkinson’s disease (PD). Loss of cholinergic projections to cortical, thalamic and midbrain regions have been associated with impairments in gait and postural control and a propensity for falls. We previously demonstrated that loss of cortical cholinergic inputs and the resulting impairments in attentional control ‘unmask’ gait and postural risk factors and thus yielded falls in rats with striatal dopamine loss (Kucinski et al., 2013). For this research we developed a new behavior task for the assessment of gait, postural control, and fall propensity (Michigan Complex Motor Control Task; MCMCT). Here, to determine the contributions of the PPN cholinergic projection system to complex movement control, we also lesioned the cholinergic pars compacta (posterior) division of the PPN by infusing anti-ChAT saporin-coupled immunotoxin. Rats received these lesions either in combination with BF cholinergic (192-IgG-saporin) or dorsomedial striatal dopamine loss (6-OHDA), or all three lesions together (“triples”). MCMCT performance by triples was characterized by more falls than in rats with just PPN lesions, PPN plus striatal dopamine loss, or rats with loss of both BF and PPN cholinergic neurons. High fall rates in triples persisted throughout the 20-day MCMCT testing sequence, indicating that daily practice did not improve the interactions between loss of attentional control and gait and postural deficits that underlie falls. Interestingly, combined loss of BF and PPN cholinergic neurons increased falls relative to controls and single lesions, suggesting that ascending cholinergic PPN loss sufficiently dysregulates striatal dopamine input for BF cholinergic cell loss to ‘unmask’ the impact of the former on striatal dysfunction. Finally, PPN cholinergic cell loss resulted in ballistic postural (recovery) movements and slip-triggered switches to asymmetrical gait. Such behavior was previously observed in rats after electrolytic lesions of the PPN region, considered a model of “Parkinsonian festination” (Cheng et al., 1981) and it may assist in maintaining balance by stabilizing the center of gravity. Collectively, our findings support the hypothesis that PPN cholinergic projections contribute to the mediation of gait symmetry and postural control, and when lesioned in combination with forebrain cholinergic and dopaminergic system, results in profound impairments in the control of complex movements. This research was supported by the Michael J. Fox Foundation.
134.02 Memory and cholinergic impairment using a new approach of bilateral lesion of rat cholinergic basal forebrain
featuring IT-01 192-IgG-SAP (poster; Sunday, Nov. 16, 8:00 AM – 12:00 PM)
158.02 Spinal antinociceptive effect of gastrin releasing peptide (GRP) via GABAergic inhibitory interneurons expressing the GRP receptor (GRPR)
featuring IT-40 Bombesin-SAP (poster; Sunday, Nov. 16, 8:00 AM – 12:00 PM)
168.07 C1 neurons excite A5 noradrenergic neurons during hypoxia condition
featuring IT-03 Anti-DBH-SAP (poster; Sunday, Nov. 16, 8:00 AM – 12:00 PM)
177.10 The role of acetylcholine in learning: Cholinergic MSDB lesions retard trace eyeblink conditioning and decrease adult neurogenesis
featuring IT-01 192-IgG-SAP (poster; Sunday, Nov. 16, 8:00 AM – 12:00 PM)
211.25 Prefrontal cholinergic overload and attentional capacities in aging
featuring IT-01 192-IgG-SAP (poster; Sunday, Nov. 16, 1:00 PM – 5:00 PM)
265.05 Lesions of hindbrain catecholaminergic projections to nucleus accumbens, bed nucleus of the stria terminalis, lateral parabrachial nucleus or locus coeruleus do not impair glucoprivic feeding
featuring IT-03 Anti-DBH-SAP (poster; Sunday, Nov. 16, 1:00 PM – 5:00 PM)
263.06 Assessing removal of illumination as a signal: Effects of loss of basal forebrain corticopetal cholinergic neurons
featuring IT-01 192-IgG-SAP (poster; Sunday, Nov. 16, 1:00 PM – 5:00 PM)
263.16 Interactions between noncholinergic basal forebrain neurons and muscarinic receptors in attentional processing
featuring IT-32 GAT1-SAP (post; Sunday, Nov. 16, 1:00 PM – 5:00 PM)
267.30 Selective ablation of mu opioid receptor expressing gaba neurons in the rostromedial tegmental nucleus promotes ethanol intake
featuring IT-12 Dermorphin-SAP (poster; Sunday, Nov. 16, 1:00 PM – 5:00 PM)
295.14 Investigating the potential of stem cell based therapy in an immunotoxin mouse model of Alzheimer’s disease
featuring IT-16 mu p75-SAP (poster; Monday, Nov. 17 8:00 AM – 12:00 PM)
307.25 Activity mediated by neurolipid (CB1 and LPA1) and neuropeptide (GAL1) receptors in a rat model with cholinergic basal forebrain lesion
featuring IT-01 192-IgG-SAP (poster; Monday, Nov. 17 8:00 AM – 12:00 PM)
327.08 Development of morphine analgesic tolerance is modulated by spinal P2X7 receptors
featuring IT-33 Mac-1-SAP (rat) (poster; Monday, Nov. 17 8:00 AM – 12:00 PM)
352.03 Correlation between hemodynamics and neuronal activity during altered brain states
featuring IT-01 192-IgG-SAP (poster; Monday, Nov. 17 8:00 AM – 12:00 PM)
452.13 Hindbrain catecholaminergic projections to the paraventricular nucleus are required for activation of glutamatergic terminals by glycemic challenges
featuring IT-03 Anti-DBH-SAP (poster; Monday, Nov. 17 1:00 PM – 5:00 PM)
453.13 Interleukin-1 receptor-expressing cells in the arcuate hypothalamus mediate peripheral interleukin-1-induced hypophagia
featuring Custom Conjugations (poster; Monday, Nov. 17 1:00 PM – 5:00 PM)
463.19 Spatial long-term memory and modulation of NMDA receptor subunit expression in medial septal immunolesioned rats
featuring IT-01 192-IgG-SAP; IT-32 GAT1-SAP (poster; Monday, Nov. 17 1:00 PM – 5:00 PM)
542.20 Vagus nerve stimulation dependent enhancement of cortical plasticity requires cholinergic innervation of the cortex
featuring IT-01 192-IgG-SAP (poster; Tuesday, Nov. 18, 8:00 AM – 12:00 PM)
543.01 Immunolesions of melanopsin receptive neurons in the adult Pekin drake attenuates the hormonal reproductive axis
featuring IT-44 Melanopsin-SAP (poster; Tuesday, Nov. 18, 8:00 AM – 12:00 PM)
543.11 Involvement of kndy neurons in luteinizing hormone surges induced by steroids
featuring IT-63 NK3-SAP (poster; Tuesday, Nov. 18, 8:00 AM – 12:00 PM)
627.07 Properties of recombinant isolectin B4 (IB4): Binding and immunostaining
featuring IT-10 IB4-SAP (poster; Tuesday, Nov. 18, 1:00 PM – 5:00 PM)
640.10 Cholinergic regulation of aromatase in brain
featuring IT-01 192-IgG-SAP (poster; Tuesday, Nov. 18, 1:00 PM – 5:00 PM)
643.10 Medullary catecholaminergic (CA) neurons modulate hypoxic ventilatory response in neonatal rats (P7-8)
featuring IT-03 Anti-DBH-SAP (poster; Tuesday, Nov. 18, 1:00 PM – 5:00 PM)
652.05 The role of the supramammillary area in spatial learning and memory
featuring IT-01 192-IgG-SAP (poster; Tuesday, Nov. 18, 1:00 PM – 5:00 PM)
692.21 Impairments in gait, posture and complex movement control in rats modeling the multi-system, cholinergic-dopaminergic losses in PD [read abstract]
featuring IT-42 Anti-ChAT-SAP (poster; Wednesday, Nov. 19, 8:00 AM – 12:00 PM)
748.01 The role of the basal forebrain cholinergic neurons in cued extinction memory
featuring IT-01 192-IgG-SAP (poster; Wednesday, Nov. 19, 8:00 AM – 12:00 PM)
749.20 Is selective hippocampal cholinergic deafferentation sufficient to produce temporally graded retrograde amnesia?
featuring IT-01 192-IgG-SAP (poster; Wednesday, Nov. 19, 8:00 AM – 12:00 PM)
670.03 Chronic oxotremorine treatment ameliorates depressive phenotype in a rodent model of Alzheimer’s disease
featuring IT-01 192-IgG-SAP (nanosymposium; Wednesday, Nov. 19, 8:30 AM – 8:45 AM)
789.21 The galantamine prodrug, Memogain®, reverses deficits in hippocampal neurogenesis associated with the loss of basal forebrain cholinergic neurons
featuring IT-01 192-IgG-SAP (poster; Wednesday, Nov. 19, 1:00 PM – 5:00 PM)
800.09 The effects of targeted intracerebral saporin injection on recovery from stroke
featuring IT-16 mu p75-SAP (poster; Wednesday, Nov. 19, 1:00 PM – 5:00 PM)
834.08 Contribution of hindbrain catecholamine neurons to orexin-induced feeding
featuring IT-03 Anti-DBH-SAP (poster; Wednesday, Nov. 19, 1:00 PM – 5:00 PM)
DP09.04 The effects of targeted intracerebral saporin injection on recovery from stroke
featuring IT-16 mu p75-SAP (dynamic poster; Wednesday, Nov. 19, 1:00 PM – 5:00 PM)
266.15 Role of nonpeptidergic subset of primary afferent neurons in inflammatory hypernociception in mice.
featuring IT-10 IB4-SAP (Poster; Sunday, November 10, 3:00 pm – 4:00 pm)
274.01 Ablation of arcuate KNDy neurons amplifies the LH surge in steroid-primed, ovariectomized rats.
featuring IT-63 NK3-SAP (Poster; Sunday, November 10, 1:00 pm – 2:00 pm)
288.02 Loss of medial prefrontal cortical cholinergic projections increases preference for an immediately available reward in a delay discounting task.
featuring IT-01 192-IgG-SAP (Poster; Sunday, November 10, 2:00 pm – 3:00 pm)
353.09 Spatial processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets.
featuring IT-15 ME20.4-SAP (Poster; Monday, November 11, 8:00 am – 9:00 am)
45.12 Selective basal forebrain cholinergic deficits reduce glucose metabolism, cholinergic and GABAergic system in the cingulate cortex.
featuring IT-01 192-IgG-SAP (Poster; Saturday, November 9, 4:00 pm – 5:00 pm)
461.10 Descending noradrenergic control of conditioned pain modulation and postoperative pain trajectory in rats.
featuring IT-03 Anti-DBH-SAP (Poster; Monday, November 11, 2:00 pm – 3:00 pm)
467.12 Neuroprotection with gonadal steroids following partial motoneuron depletion: Dependence on steroid receptor activation and hormone action at the target musculature.
featuring IT-03 Anti-DBH-SAP (Poster; Monday, November 11, 4:00 pm – 5:00 pm)
574.20 The anterior claustrum and flexible behavior in the rat: A comparison of NMDA and dynorphin-saporin lesions.
featuring IT-68 Dynorphin-SAP (Poster; Tuesday, November 12, 11:00 am – 12:00 pm)
599.01 Increased hippocampal neurogenesis and prolonged amelioration of memory deficits by chronic oxotremorine treatment in a rodent model of Alzheimer’s disease.
featuring IT-01 192-IgG-SAP (Nanosymposium; Tuesday, November 12, 1:00 pm – 1:15 pm)
623.12 The effect of noradrenaline depletion on motor impairment and dopamine cell loss in a rat model of Parkinson’s disease.
featuring IT-03 Anti-DBH-SAP (Poster; Tuesday, November 12, 4:00 pm – 5:00 pm)
639.04 Effect of medial prefrontal subregions electrical stimulation on the neuronal activity of the primary visual cortex and basal forebrain.
featuring IT-16 mu p75-SAP (Poster; Tuesday, November 12, 4:00 pm – 5:00 pm)
642.11 Male and female mice use distinct spinal immune cells to mediate chronic pain.
featuring IT-06 Mac-1-SAP mouse (Poster; Tuesday, November 12, 1:00 pm – 2:00 pm)
699.04 CD4+ T lymphocytes interact with microglia to modulate hippocampal neurogenesis. [Read Abstract]
D Khan, E Owens, M Zaben, S B Dunnett, W P Gray,
featuring IT-33 Mac-1-SAP rat (Poster; Wednesday, November 13, 11:00 am – 12:00 pm)
712.19 Investigating the potential of stem cell based therapy in an immunotoxin mouse model of Alzheimer’s disease.
featuring IT-16 mu p75-SAP (Poster; Wednesday, November 13, 10:00 am – 11:00 am)
717.18 Activation of NF-kappa κB signaling in the hippocampus without cholinergic input was aggravated by chronic stress .
featuring IT-01 192-IgG-SAP (Poster; Wednesday, November 13, 9:00 am – 10:00 am)
757.04 Compensatory feeding after reversing dehydration-anorexia: Is it analogous to glucoprivic or food deprivation-induced feeding?
featuring IT-03 Anti-DBH-SAP (Poster; Wednesday, November 13, 11:00 am – 12:00 pm)
854.02 Assessment of the contributions of baseline performance and prefrontal cortical cholinergic projections to orexin A-induced attentional enhancement.
featuring IT-01 192-IgG-SAP (Poster; Wednesday, November 13, 2:00 pm – 3:00 pm)