A GABAergic inhibitory microcircuit controlling cholinergic outflow to the airways
ABSTRACT GABA is the main inhibitory neurotransmitter that participates in the regulation of cholinergic outflow to the airways. We have tested the hypothesis that a monosynaptic GABAergic circuit modulates the output of airway-related vagal preganglionic neurons (AVPNs) in the rostral nucleus ambiguus by using a dual-labeling electron microscopic method combining immunocytochemistry for glutamic acid decarboxylase (GAD) with retrograde tracing from the trachea. We also determined the effects of blockade of GABAA receptors on airway smooth muscle tone. The results showed that retrogradely labeled AVPNs received a significant GAD-immunoreactive (GAD-IR) terminal input. Out of a pooled total of 3,161 synaptic contacts with retrogradely labeled somatic and dendritic profiles, 20.2% were GAD-IR. GAD-IR terminals formed significantly more axosomatic synapses than axodendritic synapses (P < 0.02). A dense population of GABAergic synaptic contacts on AVPNs provides a morphological basis for potent physiological effects of GABA on the excitability of AVPNs. GAD-IR terminals formed exclusively symmetric synaptic specializations. GAD-IR terminals were significantly larger (P < 0.05) in both length and width than unlabeled terminals synapsing on AVPNs. Therefore, the structural characteristics of certain nerve terminals may be closely correlated with their function. Pharmacological blockade of GABAA receptors within the rostral nucleus ambiguus increased activity of putative AVPNs and airway smooth muscle tone. We conclude that a tonically active monosynaptic GABAergic circuit utilizing symmetric synapses regulates the discharge of AVPNs.
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ABSTRACT: We reported pharmacological data suggesting that stimulation of the vago-vagal reflex activates noradrenergic neurons in the hindbrain that inhibit dorsal motor nucleus of the vagus (DMV) neurons projecting to the fundus, but not to the antrum [Ferreira Jr., M., Sahibzada, N., Shi, M., Panico, W., Neidringhaus, M., Wasserman, A., Kellar, K.J., Verbalis, J., Gillis, R.A., 2002. CNS site of action and brainstem circuitry responsible for the intravenous effects of nicotine on gastric tone. J. Neurosci. 22, 2764-2779.]. The purpose of this study was to use an ultrastructural approach to test the hypothesis that noradrenergic terminals form synapses with DMV fundus-projecting neurons, but not with DMV antrum-projecting neurons. A retrograde tracer, CTbeta-HRP, was injected into the gastric smooth muscle of either the fundus or the antrum of rats. Animals were re-anesthetized 48 h later and perfusion-fixed with acrolein and paraformaldehyde. Brainstems were processed histochemically for CTbeta-HRP, and immunocytochemically for either DbetaH or PNMT by dual-labeling electron microscopic methods. Most cell bodies and dendrites of neurons that were retrogradely labeled from the stomach occurred at the level of the area postrema. Examination of 482 synapses on 238 neurons that projected to the fundus revealed that 17.4+/-2.7% (n=4) of synaptic contacts were with DbetaH-IR terminals. Of 165 fundus-projecting neurons, 4.4+/-1.5% (n=4) formed synaptic contacts with PNMT-IR terminals. In contrast, the examination of 384 synapses on 223 antrum-projecting neurons revealed no synaptic contact with DbetaH-IR terminals. These data provide proof that norepinephrine containing nerve terminals synapse with DMV fundus-projecting neurons but not with DMV antrum-projecting neurons. These data also suggest that brainstem circuitry controlling the fundus differs from circuitry controlling the antrum.Autonomic Neuroscience 11/2007; 136(1-2):31-42. DOI:10.1016/j.autneu.2007.03.003 · 1.37 Impact Factor
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ABSTRACT: The prefrontal cortex selects relevant signals and suppresses irrelevant stimuli for a given task through mechanisms that are not understood. We addressed this issue using as a model system the pathways from the functionally distinct prefrontal areas 10 and 32 to auditory association cortex, and investigated their relationship to inhibitory neurons labeled for calbindin (CB) or parvalbumin (PV), which differ in mode of inhibition. Projection neurons in area 10 originated mostly in layers 2-3 and were intermingled with CB inhibitory neurons. In contrast, projections from area 32 originated predominantly in layers 5-6 among PV inhibitory neurons. Prefrontal axonal boutons terminating in layers 2-3 of auditory association cortex were larger than those terminating in layer 1. Most prefrontal axons synapsed on spines of excitatory neurons but a significant number targeted dendritic shafts of inhibitory neurons. Axons from area 10 targeted CB and PV inhibitory neurons, whereas axons from area 32 targeted PV inhibitory neurons. The preferential association of the 2 prefrontal pathways with distinct classes of inhibitory neurons at their origin and termination may reflect the specialization of area 10 in working memory functions and area 32 in emotional communication. These findings suggest diversity in inhibitory control by distinct prefrontal pathways.Cerebral Cortex 10/2007; 17 Suppl 1:i136-50. DOI:10.1093/cercor/bhm068 · 8.31 Impact Factor
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ABSTRACT: In this letter, we present an implementation of a neural microcircuit for image processing employing Hebbian-adaptive learning. The neuronal circuit utilizes only excitatory synapses to correlate action potentials, extracting the uncorrelated ones, which contain significant image information. This circuit is capable of approximating Gabor-like image filtering and other image processing functions.IEEE Transactions on Neural Networks 06/2007; 18(3):955-9. DOI:10.1109/TNN.2007.891687 · 2.95 Impact Factor