Segregation of Acetylcholine and GABA in the Rat Superior Cervical Ganglia: Functional Correlation

Abstract

Sympathetic neurons have the capability to segregate their neurotransmitters (NTs) and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh) and other classical NTs such as gamma aminobutyric acid (GABA). Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX). We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level of segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region showed larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons.

A novel sympathetic neuronal GABAergic signalling system regulates NE release to prevent ventricular arrhythmias after acute myocardial infarction

“…30 Other reports have also discussed tonic GABA inhibition on ganglionic function in the SCG. 13 Similar to previous reports, 31 we found GAD65/67-positive neurons in rat SCG slices ( Figure 1A), and GABA A Rβ 2 was expressed in both the cell body and axons of the SCG cultured neurons ( Figure 1A). However, the SCG neurons showed an uneven distribution of GAD65/67, similar to Wolff, JR's results, 32 indicating a feed-forward inhibition system inside the SCG.…”

“…However, the SCG neurons showed an uneven distribution of GAD65/67, similar to Wolff, JR's results, 32 indicating a feed-forward inhibition system inside the SCG. Diana Elinos et al 13 suggested that GABA A Rα4 subunits are mainly expressed on principle ganglion neurons and that this subunit distribution is related to the level of GABA inhibition. Diana Elinos et al 13 suggested that GABA A Rα4 subunits are mainly expressed on principle ganglion neurons and that this subunit distribution is related to the level of GABA inhibition.…”

“…Consistent with the inhibitory effect of GABA in the SCG, lentivirus knockdown of GABA A Rβ 2 resulted in a significant increase in postganglionic activity, implicating the GABA A receptor as a target. Diana Elinos et al 13 suggested that GABA A Rα4 subunits are mainly expressed on principle ganglion neurons and that this subunit distribution is related to the level of GABA inhibition. In this study, we knocked down GABA A Rβ 2 throughout the SCG without affecting the GABA A Rα4 subunit, and the data showed a thorough upregulation of sympathetic activity.…”

“…41 Additionally, the preganglionic nerves contain GABA varicosities. 13 Moreover, in various medullary structures, GABA is involved in baroreflex function and sympathetic tone that can reduce the occurrence of arrhythmias. 42 The blockade of CNS GABA A Rs in particular increases the sympathetic output to the heart.…”

“…Postganglionic neurons in the SCG are believed to be positively regulated by presynaptic acetylcholine (ACh) nerve fibres, while the other regulating mechanisms remain obscure even though several hypotheses have been raised. 11,12 For example, Wolff et al 11 suggested that neurons in the SCG releasing γ-aminobutyric acid (GABA) regulate nerve activity, while Diana Elinos et al 13 supported a different degree of ACh and GABA segregation in presynaptic ACh fibres. The common finding in all reported articles is that the SCG expresses GABA, GABA receptors and GABA synthetic enzymes 14 by which it may regulate ganglionic transmission 14 and decrease blood pressure and heart rate (HR) physiologically.…”