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Medial septum-diagonal band of Broca (MSDB) GABAergic regulation of hippocampal acetylcholine efflux is dependent on cognitive demands.
Roland JJ, Stewart AL, Janke KL, Gielow MR, Kostek JA, Savage LM, Servatius RJ, Pang KC (2014) Medial septum-diagonal band of Broca (MSDB) GABAergic regulation of hippocampal acetylcholine efflux is dependent on cognitive demands. J Neurosci 34(2):506-514. doi: 10.1523/JNEUROSCI.2352-13.2014
Summary: GABAergic and cholinergic neurons in the medial septum-diagonal band of Broca (MSDB) are both involved with spatial memory. In order to better understand the relationship between these two neuronal populations the authors administered 552.5 ng of GAT-1-SAP (Cat. #IT-32) to the MSDB of rats in several injections. Using a combination of behavioral assays and in vivo microdialysis it was shown that GAT-1-SAP lesions impaired hippocampal acetylcholine efflux as well as performance in the non-matching to position with delay test. The data indicate that GABAergic MSDB neurons are important during high memory load conditions.
Related Products: GAT1-SAP (Cat. #IT-32)
Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions.
Baxter MG, Bucci DJ (2013) Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions. Behav Neurosci 127(5):611-618 . doi: 10.1037/a0033781
Summary: This review covers twenty years of basal forebrain cholinergic lesioning. The initial use of 192-IgG-SAP (Cat. #IT-01) is discussed, as well as other immunotoxins such as GAT-1-SAP (Cat. #IT-32) and OX7-SAP (Cat. #IT-02). The findings generated by the use of 192-IgG-SAP and how those data have helped forward the understanding of how the cholinergic system functions in the basal forebrain are detailed. The authors also discuss new directions in the field.
Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), GAT1-SAP (Cat. #IT-32)
GABAergic neurons in the medial septum-diagonal band of Broca (MSDB) are important for acquisition of the classically conditioned eyeblink response.
Roland J, Janke K, Servatius R, Pang K (2014) GABAergic neurons in the medial septum-diagonal band of Broca (MSDB) are important for acquisition of the classically conditioned eyeblink response. Brain Struct Funct 219:1231-1237. doi: 10.1007/s00429-013-0560-4
Summary: The medial septum and vertical limb of the diagonal band of Broca (MSDB) are both important for learning and memory. There are strong connections between these two areas, and damage to one or the other can result in differing dysfunctions. The authors investigated how damage to GABAergic neurons in the MSDB affect acquisition of delay classical conditioning of the eyeblink response (CCER). Rats received 162 ng of GAT-1-SAP (Cat. #IT-32) into the medial septum and 130 ng of GAT-1-SAP into each diagonal band. Treated animals displayed impaired initial acquisition of the eyeblink response, indicating that MSDB GABAergic neurons modulate delay CCER – a task that is not dependent on the hippocampus.
Related Products: GAT1-SAP (Cat. #IT-32)
Infusion of GAT1-Saporin into the medial septum spares mnemonic function and impairs self-movement cue processing.
Koppen JR, Stuebing SS, Winter SS, Cheatwood JL, Wallace DG (2012) Infusion of GAT1-Saporin into the medial septum spares mnemonic function and impairs self-movement cue processing. Neuroscience 2012 Abstracts 394.25. Society for Neuroscience, New Orleans, LA.
Summary: Spatial orientation depends on multiple neural systems processing environmental and self-movement cues. Previous research has demonstrated a relationship between cholinergic function in the medial septum and processing of self-movement cues. The medial septum also sends GABAergic projections to the hippocampus that synapse on interneurons, thereby producing a strong dis-inhibitory effect on hippocampal pyramidal neurons. Initial studies using non-selective lesion techniques have supported the involvement of this system in spatial orientation; however, the development of an immunotoxin (i.e., GAT1-Saporin) that selectively targets GABAergic neurons, allows for a novel technique in which to study this relationship. The current study examined the effect of infusing GAT1-Saporin or saline into the medial septum on performance during multiple spatial tasks. Environmental and self-movement cue processing was evaluated using the food hoarding paradigm, whereas mnemonic function was evaluated using several water maze tasks. Although GAT1-Saporin spared performance on water maze tasks, impaired performance was observed when rats were restricted to using self-movement cues (i.e., testing under dark conditions) during food hoarding. The current study adds to the growing literature that supports a role for components of the septohippocampal system in self-movement cue processing during spatial navigation.
Related Products: GAT1-SAP (Cat. #IT-32)
Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function.
Koppen JR, Winter SS, Stuebing SL, Cheatwood JL, Wallace DG (2013) Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function. Brain Struct Funct 218(5):1099-1114. doi: 10.1007/s00429-012-0449-7
Summary: Both mnemonic and spatial processing are adversely affected by dementia due to Alzheimer’s disease. There is evidence to support the involvement of cholinergic systems in this deficit. In this work the authors examined how GABAergic neurons in the septohippocampus contribute to these cognitive functions. Rats received a total of 350 ng of GAT-1-SAP (Cat. #IT-32) infused into the medial septum-diagonal band of Broca. Although lesioned animals performed normally in tasks involving spatial cues, food hoarding was affected indicating that self-movement cue processing was interfered with by the loss of these GABAergic neurons.
Related Products: GAT1-SAP (Cat. #IT-32)
Role of the medial septal-diagonal band nucleus in working memory: Effects of cholinergic or GABAergic lesions on memory demand and interference
Stewart AL, Roland JJ, Servatius RJ, Pang K (2011) Role of the medial septal-diagonal band nucleus in working memory: Effects of cholinergic or GABAergic lesions on memory demand and interference. Neuroscience 2011 Abstracts 513.09. Society for Neuroscience, Washington, DC.
Summary: The medial septum and diagonal band of Broca (MSDB), a major source of afferents to the hippocampal formation, is critical for learning and memory. The primary cells comprising the septohippocampal systems are cholinergic, GABAergic and glutamatergic. Selective damage of cholinergic MSDB neurons results in mild to no impairment of spatial working memory tasks, suggesting that non-cholinergic MSDB projections are important in learning and memory. Recently, we demonstrated that GABAergic MSDB lesions impair a delayed match to position task (DNMTP) with errors suggesting enhanced proactive interference. The current study assesses the effect of manipulating the intertrial interval (ITI) and retention interval (RI) on DNMTP performance in normal rats and those with cholinergic or GABAergic MSDB damage. In addition, activation of MSDB neurons on the last day of training will be assessed. Male Sprague Dawley rats receive sham, 192-IgG saporin (192-Sap) or GAT1-saporin (GAT1-Sap) administration into the MSDB before training on a DNMTP task using a T-maze. On the sample phase of each trial, rats are forced to one arm for reinforcement. Following an RI, a choice phase allows the rats to choose from both arms. Rats are reinforced for choosing the arm not entered during the sample phase. Following the choice phase, an ITI occurs before the sample phase of the next trial. Rats are trained one session per day, 12 trials per session, and 10 sessions. In a 2 x 2 experimental design, each rat is trained on either a 0 or 60s RI and a 0 or 60s ITI. Conditions with a long RI (60 s) are designed to tax working memory, whereas conditions with a similar RI and ITI are designed to increase interference. Immunocytochemistry for c-Fos is used to assess activation of cholinergic or GABAergic MSDB neurons following the last training session. As expected, our preliminary results show that sham rats performed better on 0 s than 60 s RI (0 s = 78% correct vs 60 s = 57%, both ITI’s pooled). Analysis of the 0 s RI demonstrates that performance in conditions with different RI and ITI was better than when RI and ITI were similar (0 s RI/60 s ITI = 74% vs 0 s RI/0 s ITI = 67%). Further analysis of the 60 s RI was difficult due to the near chance performance. Rats treated with either intraseptal 192-Sap or GAT1-Sap were impaired on the 0 s RI/60s ITI condition (Sham: 85%; 192-Sap: 65%; GAT1-Sap: 72%). However, only the 192-Sap rats were impaired in the 0 s RI/0 s ITI condition (Sham: 71%; 192-Sap: 62%; GAT1-Sap: 69%). Anatomical studies are currently underway. The results of this study will further elucidate the role of MSDB neurons in two aspects of working memory: memory demand and interference.
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)
Reduced hippocampal acetylcholine efflux after medial septal-diagonal band (MSDB) GABAergic lesion is associated with impaired working memory: behavioral and neurochemical effects of physostigmine.
Roland JJ, Stewart AL, Savage LM, Servatius RJ, Pang KCH (2011) Reduced hippocampal acetylcholine efflux after medial septal-diagonal band (MSDB) GABAergic lesion is associated with impaired working memory: behavioral and neurochemical effects of physostigmine. Neuroscience 2011 Abstracts 513.10. Society for Neuroscience, Washington, DC.
Summary: The medial septum provides cholinergic innervation of the hippocampus and changes in hippocampal acetylcholine (ACh) have been tied to memory; deficits and enhancements in memory are correlated with decreases or increases of ACh, respectively. Damage of GABAergic MSDB neurons impaired spatial working memory in a delayed non-match to position task with a 30-s retention interval (DNMTP). Interestingly, lesions reduced maze activated hippocampal ACh efflux, but did not alter basal hippocampal ACh efflux. The current study has two aims. First, is performance impaired and ACh efflux reduced in a non-match to position task (NMTP) with a 0-s retention interval following GABAergic MSDB damage? Second, is performance on DNMTP improved by enhancing hippocampal ACh efflux? Male Sprague-Dawley rats received intraseptal PBS or GAT1-saporin (to damage GABAergic neurons) and a ventral hippocampal microdialysis cannula to assess ACh efflux. In Exp. 1, rats were trained on NMTP for 10 days and received microdialysis on either day 2 (early) or day 9 (late). GAT1-saporin rats were not behaviorally impaired and hippocampal ACh efflux was similar in both treatment groups. These results suggest that performance with a short retention interval (NMTP) is more independent of MSDB influences than training with a long retention interval (DNMTP). Exp. 2 was designed to determine whether the reduced ACh efflux is a critical factor in impaired DNMTP performance in rats with GABAergic MSDB damage. In Exp. 2, all rats will receive 10 day of DNMTP training. On days 8 and 9, rats will be administered (i.c.v.) either saline or the acetylcholinesterase inhibitor, physostigmine (5μg/μl). The effects of physostigmine on behavioral performance and hippocampal ACh efflux will be determined. We predict that physostigmine will increase ACh efflux but not improve behavior, suggesting that hippocampal ACh is not important for DNMTP performance. However, support that both MSDB cholinergic and GABAergic neurons are important for DNMTP performance would be seen if physostigmine increases ACh efflux and enhances DNMTP performance. In summary, damage of MSDB GABAergic neurons modulates hippocampal ACh efflux during performance of a working memory task. Whether hippocampal ACh release plays a critical role in impaired working memory will be answered by these studies.
Related Products: GAT1-SAP (Cat. #IT-32)
The role of medial septal/diagonal band GABAergic neurons in proactive interference: Effects of selective immunotoxic lesions in latent inhibition
Sinha SP, Roland JJ, Servatius RJ, Pang KCH (2011) The role of medial septal/diagonal band GABAergic neurons in proactive interference: Effects of selective immunotoxic lesions in latent inhibition. Neuroscience 2011 Abstracts 199.22. Society for Neuroscience, Washington, DC.
Summary: The medial septum/diagonal band (MSDB) is a critical structure for learning and memory, yet the functional contributions of its individual neuronal populations (including cholinergic, GABAergic, glutamatergic and peptidergic cells) are still being characterized. Recent studies have implicated a contributing role for the GABAergic MSDB neuronal population, as selective immunotoxic GABAergic lesions of the MSDB (with GAT1-saporin) produce behavioral impairments in spatial and instrumental tasks. Compared to intact controls, rats with GABAergic MSDB lesions are impaired in learning new spatial locations in a delayed match to position procedure and also exhibit a slower rate of extinguishing a previously acquired avoidance response – behaviors that are consistent with an exacerbation of proactive interference. To further establish the role of these neurons in proactive interference, this study examined the effects of selective GABAergic MSDB lesions in latent inhibition (LI) of the classically conditioned eyeblink response. LI in delay eyeblink conditioning is a phenomenon in which pre-exposure to the conditioned stimulus (CS) interferes with the subjects’ ability to subsequently associate the CS with an unconditioned stimulus (US), resulting in slower acquisition of the conditioned response (CR). We hypothesized that if damage of GABAergic MSDB neurons increases proactive interference, then rats with selective lesions of these neurons would show facilitated LI. Male Sprague-Dawley rats (n=18) were administered either phosphate-buffered saline or GAT1-saporin via intracranial injection into the MSDB. After 7-10 days of recovery, electrodes were implanted into the upper eyelids of the rats for delivery of US and EMG recording. Conditioning began after another 5-7 days of recovery, with Day 1 consisting of 30 minutes of acclimation to the conditioning context. Day 2 began with either 30 presentations of the CS (82dB, 500ms white noise, 25 – 35s ITI) or context pre-exposure of equal duration, followed immediately by 100 paired CS-US trials (82 dB, 500ms white noise co-terminating with a 10V, 10ms square-wave stimulus). In preliminary results, intraseptal GAT1-saporin did not alter CR acquisition in context pre-exposed rats. Rats with GABAergic MSDB lesions continued to exhibit latent inhibition. These preliminary results do not support the idea that damage of GABAergic MSDB neurons increase proactive interference of the classically conditioned eyeblink response. Future studies will examine whether manipulations of the number of CS pre-exposures would facilitate LI in rats with GABAergic MSDB lesions.
Related Products: GAT1-SAP (Cat. #IT-32)
A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response.
Radley JJ, Sawchenko PE (2011) A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response. J Neurosci 31(26):9683-95. doi: 10.1523/JNEUROSCI.6040-10.2011
Summary: In order to better understand how response to emotional stress is regulated, the authors injected 114 ng of GAT-1-SAP (Cat. #IT-32) into each side of the anterior bed nucleus of the stria terminalis. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results suggest that medial prefrontal cortex and hippocampal formation influences on stress regulation use the same access to modulate emotional stress rather than having parallel networks.
Related Products: GAT1-SAP (Cat. #IT-32), Mouse IgG-SAP (Cat. #IT-18)
Role of the septohippocampal GABAergic system in spatial orientation
Koppen JR, Winter SS, Cheatwood JL, Wallace DG (2010) Role of the septohippocampal GABAergic system in spatial orientation. Neuroscience 2010 Abstracts 806.16/KKK21. Society for Neuroscience, San Diego, CA.
Summary: Spatial orientation depends on the integrity of multiple neural systems. For example, during the progression of Alzheimer’s Disease, degeneration of the basal forebrain is associated with cognitive impairments including episodes of wandering. The medial septum projects both cholinergic and GABAergic fibers into the hippocampus. Research and therapies have typically focused on enhancing function of the cholinergic component; however, the GABAergic component has also been shown to contribute to hippocampal function. Previous attempts to characterize the role of the GABAergic system in spatial orientation involved non-selective lesion techniques in combination with the water maze task have failed to characterize the nature of the deficit mediating the impaired performance. Development of GAT1-Saporin immunotoxin provides a novel tool to selectively destroy GABAergic neurons in the medial septum. The current study examined the effects of injecting GAT1-Saporin or saline (sham lesion) into the medial septum on spatial orientation using the food-hoarding paradigm. The food-hoarding paradigm involves training rats to search for food pellets on a large circular table and carrying the food pellet directly to a visible refuge. Three probes dissociate the use of environmental and self-movement cues: 1) Hidden probe involved placing the refuge below the surface of the table, limiting rats to use distal environmental or self-movement cues to locate the refuge; 2) Dark Probe involved using the hidden refuge with the room lights off, limiting rats to use self-movement cues to locate the refuge; 3) New probe involved placing the hidden refuge on the opposite side of table, placing environmental and self-movement cues in conflict. Both sham and GAT1-Saporin rats were accurate in returning to the refuge during the Hidden probe. Only sham rats were accurate in carrying food to the refuge during the Dark probe. During the New probe, both groups initially carried the food pellet to the former refuge location. Although sham rats consistently carried the food pellet to the new refuge location after their initial error, GAT1-Saporin rats continued to perseverate to the former refuge location. The current study demonstrates a role for the septohippocampal GABAergic system in spatial orientation related to processing self-movement cues.
Related Products: GAT1-SAP (Cat. #IT-32)