Local GABAergic modulation of acetylcholine release from the cortex of freely moving rats

Abstract

Cortical perfusion with GABA agonists and antagonists modulates the spontaneous release of cortical acetylcholine and GABA in freely moving rats. Twenty-four hours after implantation of a dialysis fibre, cerebral cortex spontaneously released acetylcholine (3.8 +/- 0.2 pmol/10 min) and GABA (6.6 +/- 0.4 pmol/10 min) at a stable rate. Local administration of GABA (1 or 5 mM) or the GABAA agonist muscimol (25 or 50 microM) had no effect on the spontaneous release of acetylcholine. However, bicuculline (1-25 microM), a GABAA antagonist, added to the dialysis perfusate, elicited a concentration-dependent increase of acetylcholine release to approximately double that of control. This effect of bicuculline (25 microM) was completely prevented by coperfusion with muscimol (50 microM). Local administration of the GABAB receptor agonist baclofen (10 or 50 microM) elicited a concentration-dependent increase in spontaneous acetylcholine release with a maximal increase of about 60%. Intracortical administration of baclofen also decreased the spontaneous release of GABA. The GABAB receptor antagonist CGP 35348 (1 mM), administered alone for 20 min through the dialysis fibre, was without effect on spontaneous acetylcholine release; however, it completely blocked both the baclofen-induced increase in acetylcholine release and the decrease in GABA release. These results suggest that cortically released GABA exerts a tonic influence on cholinergic activity.

Interactions between histaminergic and cholinergic systems in learning and memory

“…1). Histamine activates cortical H 3 receptors, which are likely localized on GABA interneurons, and inhibits the release of cortical ACh through a GABAergic mechanism [14,48,50]. On the other hand, histaminergic projections to NBM exert a tonic influence on cortical cholinergic activity, depolarizing cholinergic cell bodies through activation of H 1 receptors [22,70], thus increasing ACh release from the cortex [22].…”

“…The most simple hypothesis is that GABA activated GABA A receptors localized on cholinergic nerve endings, thus reducing ACh release. Experimental evidence suggests that the cortical GABAergic system exerts a tonic inhibition of spontaneous release of ACh from the cortex, and that this inhibitory tone is maximal [49]. This could elucidate why neither histamine nor either of H 3 receptor agonists altered spontaneous ACh release [14], much of which is tetrodotoxin sensitive [14].…”

Functional involvement of the cerebral cortex following paramedian bithalamic infarction

“…This reduction in SAI may be explained by an inhibition in ACh release due to the enhancement of GABAergic activity. GABA is known to affect cholinergic transmission at multiple central nervous system levels (Giorgetti et al, 2000). GABA A antagonists enhance release of ACh at the level of the cerebral cortex (Diez-Ariza, Garcia-Alloza, The data of the control group are reported in terms of 99% prediction intervals.…”

“…Legend: LH, left hemisphere; RH, right hemisphere; 1°, first examination; 2°, second examination; CMCT, central motor conduction time; RMT, resting motor threshold; AMT, active motor threshold; MSO, maximum stimulator output; MEP, motor evoked potential; CSP, cortical silent period; SICI, short latency intracortical inhibition; ICF, intracortical facilitation; SAI, short latency afferent inhibition; CMAP, compound motor action potential. Lasheras, Del Rio, & Ramirez, 2002;Giorgetti et al, 2000) and at the forebrain level (Vasquez & Baghdoyan, 2003); GABA A receptors are localized on forebrain cholinergic neurons projecting to the cortex (Zaborszky, Heimer, Eckenstein, & Leranth, 1986), and their activation results in inhibition (Khateb et al, 1998). It has been recently demonstrated (Di Lazzaro et al, 2005b) that the administration of lorazepam produces a significant increase in SICI and a significant decrease of SAI in normal subjects.…”

A computational model of mechanisms controlling experience-dependent reorganization of representational maps in auditory cortex

“…Auditory cortical sensitivities can be substantially modified by blocking the effects of GABA (Foeller, Vater, & Kossl, 2000;Schulze & Langner, 1999;J. Wang, Caspary, & Salvi, 2000), providing support for Dykes's (1997) proposal that GABAergic modulation can significantly affect cortical reorganization (see also Giorgetti et al, 2000;Jiminez-Capdeville, Dykes, & Myasnikov, 1997). The effects of peptides on auditory cortical plasticity, if any, are unknown.…”