Targeting Topics 12q1

Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats.

Abbott SB, Stornetta RL, Coates MB, Guyenet PG.

J Neurosci 31(45):16410-16422, 2011.

Neurons in the retrotrapezoid nucleus (RTN) are involved in the CO2-dependent control of breathing in conscious and anesthetized rats. In this work the authors specifically examined Phox2b-expressing glutaminergic neurons in the RTN. Rats received 44 ng of DBH-SAP (Cat. #IT-03) into the lateral horn of the second thoracic segment in order to eliminate C1 neurons that project to the spinal cord. The data demonstrate regulation of lung ventilation by RTN-Phox2b neurons, and also that these neurons are not rhythmogenic in adults.

Impaired Visual Search in Rats Reveals Cholinergic Contributions to Feature Binding in Visuospatial Attention.

Botly LC, De Rosa E.

Cereb Cortex 22(10):2441-2453, 2012.

Previous work established the role of acetylcholine from the nucleus basalis magnocellularis in attentional processing and visuospatial attention. In order to investigate the necessity of cortical cholinergic input for support of feature binding in visuospatial attention the authors administered bilateral intraparenchymal injections of 192-IgG-SAP (Cat. #IT-01, 4 injections, 40 ng per injection). Lesioned animals took longer to locate targets during type-specific search trials, demonstrating that cholinergic input influences feature binding during visuospatial attention tasks.

Recognition of novel objects and their location in rats with selective cholinergic lesion of the medial septum.

Cai L, Gibbs RB, Johnson DA.

Neurosci Lett 506(2):261-265, 2012.

This work examined object recognition and object location recognition as specific components of memory. Rats received 0.22 μg of 192-IgG-SAP (Cat. #IT-01) infused into the medial septum followed by testing in novel object recognition (NOR) and object location recognition (OLR) models. Substantial decreases in choline acetyltransferase activity in the hippocampus and frontal cortex produced no difference in NOR but caused a significant impairment in OLR – highlighting the role that septo-hippocampal cholinergic projections play in OLR.

Reassessment of the structural basis of the ascending arousal system.

Fuller P, Sherman D, Pedersen NP, Saper CB, Lu J.

J Comp Neurol 519(5):933-956, 2011.

Traditional thought has been that electroencephalogram activity is mainly generated by the thalamo-cortical system. In this work the authors investigated the effects of basal forebrain lesions on various measurments of wakefulness. Rats received 4 50 ng injections of 192-IgG-SAP (Cat. #IT-01) into the basal forebrain. The effects of these lesions showed that the parabrachial nucleus/precoeruleus region projection relayed by the basal forebrain to the cerebral cortex plays a critical role in behavioral and electrocortical arousal.

Depletion of Endogenous Noradrenaline Does Not Prevent Spinal Cord Plasticity Following Peripheral Nerve Injury.

Hayashida K, Peters CM, Gutierrez S, Eisenach JC.

J Pain 13(1):49-57, 2012.

The authors examined what involvement noradrenergic fibers in the spinal cord have in neuronal and glial plasticity associated with neuropathic pain states. Rats received 5 μg intrathecal injections of anti-DBH-SAP (Cat. #IT-03). Lesioned animals did not display altered mechanical withdrawal thresholds, but L5-L6 spinal nerve ligation in these animals caused enhanced mechanical hypersensitivity and analgesia induced by intrathecal clonidine. The data suggest that endogenous noradrenaline may play an inhibitory role on glial activation.

Redefining the components of central CO2 chemosensitivity – towards a better understanding of mechanism.

Huckstepp RT, Dale N.

J Physiol 589(Pt 23):5561-5579, 2011.

This review discusses advances in the field of CO2 chemosensitivity over the past few years. Discussion of the role that locus coeruleus (LC) neurons play in this process describe the use of anti-DBH-SAP (Cat. #IT-03) to reduce the hypercapnic ventilatory response. Data from these and other experiments support a role of the LC in modulation of the ventilatory response to hypercapnia.

Cholinergic Control in Developing Prefrontal-Hippocampal Networks.

Janiesch PC, Kruger HS, Poschel B, Hanganu-Opatz IL.

J Neurosci 31(49):17955-17970, 2011.

In this work the authors examined the role of acetylcholine in the maturation of cognitive processing due to oscillatory rhythms entraining neuronal networks. Rats received 50 ng of 192-IgG-SAP (Cat. #IT-01) into each lateral ventricle, or 25 ng directly into the medial septum. Among other results, cholinergic input was shown to reach the prefrontal cortex toward the end of the first postnatal week, initially targeting GABAergic neurons. Reduction of this activity by lesioning cholinergic neurons may cause global diminishment of neocortical activity.

MAP kinases couple hindbrain-derived catecholamine signals to hypothalamic adrenocortical control mechanisms during glycemia-related challenges.

Khan AM KKL, Sanchez-Watts, Ponzio TA, Kuzmiski JB, Bains JS, Watts AG.

J Neurosci 31(50):18479-18491, 2011.

This work uses in vivo and ex vivo techniques to clarify how hypothalamic afferent pathways use intracellular mechanisms to modulate glycemia related adrenocortical responses. Rats received 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results establish a relationship between neurons from nutrient-sensing regions and intracellular mechanisms in hypothalamic corticotropin-releasing hormone neuroendocrine neurons.

Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids.

Liu XY, Liu ZC, Sun YG, Ross M, Kim S, Tsai FF, Li QF, Jeffry J, Kim JY, Loh HH, Chen ZF.

Cell 147(2):447-458, 2011.

Recent work has begun to define the different pathways used by itch and pain. This study was designed to investigate whether opioids cause the itch sensation by gastrin releasing peptide receptor activation. Mice received intrathecal injections of bombesin-SAP (Cat. #IT-40) in order to investigate the coexpression of various signaling molecules in the spinal cord. Blank-SAP (Cat. #IT-21) was used as a control. The data suggest that opioid-induced itch is independent of opioid analgesia, and is controlled through a mu-opioid receptor isoform.

Minireview: The value of looking backward: the essential role of the hindbrain in counterregulatory responses to glucose deficit.

Ritter S, Li AJ, Wang Q, Dinh TT.

Endocrinology 152(11):4019-4032, 2011.

This review examines work addressing how particular glucose-sensing cells function in glucoregulation under specific physiological or pathological conditions. There are specific populations of norepinephrine (NE) and epinephrine (E) neurons in the hindbrain that mediate these responses. The use of anti-DBH-SAP (Cat. #IT-03) to eliminate selective NE/E subgroups without disrupting basic functions is discussed.

Control of the central chemoreflex by A5 noradrenergic neurons in rats.

Taxini CL, Takakura AC, Gargaglioni LH, Moreira TS.

Neuroscience 199:177-186, 2011.

The A5 group of noradrenergic neurons in the ventrolateral pons is involved in the control of sympathetic and respiratory networks. Using anti-DBH-SAP (Cat. #IT-03) the authors eliminated TH+ neurons in order to clarify which aspects of respiration are modulated by A5 neurons. Rats received bilateral 4.2-ng injections of the toxin into the A5 region. The results suggest that A5 noradrenergic neurons are involved in control of mean arterial pressure, splanchnic sympathetic nerve activity, and phrenic nerve activity.