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This Article Full Text Full Text (PDF) All Versions of this Article: 582/2/539    most recent jphysiol.2007.133223v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Park, J. B. Articles by Stern, J. E. Search for Related Content PubMed PubMed Citation Articles by Park, J. B. Articles by Stern, J. E. Related Collections Neuroscience

¹ Department of Psychiatry, Genome Research Institute, University of Cincinnati, Cincinnati, OH 45247, USA

The inhibitory neurotransmitter GABA plays a key role in the modulation of paraventricular nucleus (PVN) neuronal excitability and sympathoexcitatory outflow, under both physiological and pathological conditions. In addition to mediating conventional synaptic transmission (phasic inhibition), GABA_A receptors of distinct biophysical, molecular and pharmacological properties have been recently found to underlie a slower, persistent form of inhibition (tonic inhibition). Whether the ‘tonic’ inhibitory modality is present in presympathetic PVN neurons, and what its role is in modulating their activity is at present unknown. Here, we combined tract-tracing techniques with patch-clamp electrophysiology to address these questions. Recordings obtained from PVN-RVLM (rostral ventrolateral medulla) projecting neurons show that besides blocking GABA_A-mediated inhibitory postsynaptic currents (IPSCs, I_phasic), the GABA_A receptor blockers bicuculline and picrotoxin caused an outward shift in the holding current (I_tonic). Conversely, the high affinity GABA_A blocker gabazine blocked I_phasic without affecting I_tonic. THIP, a GABA_A receptor agonist that preferentially activates - over -containing receptors, enhanced the magnitude of I_tonic. Our results also indicate that during conditions of strong and/or synchronous synaptic activity, I_tonic may be activated by spillover of synaptically released GABA. Blockade of I_tonic induced membrane depolarization, increased firing activity, and enhanced the input–output function of PVN-RVLM neurons. Altogether, our results support the presence of a persistent GABA_A-mediated inhibitory modality in presympathetic PVN neurons, which plays a major role in modulating their excitability and firing activity.

(Received 22 March 2007; accepted after revision 3 May 2007; first published online 10 May 2007)
Corresponding author J. E. Stern: Department of Psychiatry, University of Cincinnati, GRI-A Room 241, 2170 E. Galbraith Road, Cincinnati, OH 45237, USA. Email: javier.stern{at}uc.edu