GABA synapses formed in vitro by local axon collaterals of nucleus accumbens neurons.
GABAergic medium-spiny neuron axons not only form the principal projections of the nucleus accumbens (nAcc) but also branch locally in a dense network overlapping their own dendrites, suggesting that their recurrent synapses mediate the major information processing functions of the nAcc. We used postnatal nAcc cultures to study these synapses individually. In culture, as in the intact nAcc, medium-spiny neurons account for over 95% of the cells and are GABAergic. Strikingly, these neurons showed a spike afterhyperpolarization (AHP) that was largely blocked by the GABAA antagonist bicuculline. The bicuculline-sensitive AHP occurred without or with latency, and met criteria for monosynapticity; consistent with this, dye fills showed the presence of recurrent axons and a low incidence of dye coupling. Blockade of Ca2+ influx eliminated this autaptic PSP, while TTX almost completely eliminated it, indicating that it is due to exocytic GABA release principally at axodendritic contacts. While blocking GABAB receptors had no direct effect on the autaptic PSP, activating these receptors with baclofen produced presynaptic inhibition, as well as directly mediated hyperpolarization; together, these actions increased the signal-to-noise ratio in the cellular response to synaptic inputs. Bicuculline also increased the signal-to-noise ratio; in addition, it induced burst firing and depolarization inactivation. In contrast, the indirect GABA agonist flurazepam and the GABA uptake blocker nipecotic acid each enhanced autaptic PSPs. Since autapses formed in vitro appear to be functionally equivalent to synapses between neighboring medium-spiny neurons that receive similar inputs, these results bear on the function of intrinsic GABA synapses in the intact nAcc. Thus, intrinsic GABA synapses are likely to regulate the signal-to-noise ratio in nAcc information processing and may be important targets for the modulatory actions of endogenous neurotransmitters and drugs.
Shi
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WX
Department of Psychiatry, Columbia University, New York, New York 10032.
Rayport
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D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline