RT Journal Article
SR Electronic
T1 Differential Actions of Serotonin, Mediated by 5-HT<sub>1B</sub>and 5-HT<sub>2C</sub> Receptors, on GABA-Mediated Synaptic Input to Rat Substantia Nigra Pars Reticulata Neurons <em>In Vitro</em>
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7566
OP 7573
DO 10.1523/JNEUROSCI.16-23-07566.1996
VO 16
IS 23
A1 Ian M. Stanford
A1 Michael G. Lacey
YR 1996
UL http://www.jneurosci.org/content/16/23/7566.abstract
AB The ability of serotonin to modulate GABA-mediated synaptic input to substantia nigra pars reticulata (SNr) neurons was investigated with the use of whole-cell patch-clamp recording from slices of rat midbrain. Fast evoked GABAA receptor-mediated synaptic currents (IPSCs) were attenuated reversibly ∼60% by serotonin, which also caused an inward current with reversal potential of −25 mV. This inward current was blocked by the 5-HT2 receptor antagonist ritanserin, whereas the IPSC depression was blocked by the 5-HT1B receptor antagonist pindolol. The amplitude ratio of IPSC pairs (50 msec interpulse interval) was enhanced by serotonin (in ritanserin) and also by the GABAB receptor agonist baclofen (which also depressed the IPSC), consistent with a presynaptic site of action in both cases. In contrast, spontaneous tetrodotoxin-sensitive GABAA synaptic currents (sIPSCs) were increased in frequency by serotonin (an action that was sensitive to ritanserin, but not pindolol) but reduced in frequency by baclofen. SNr neurons therefore receive inhibitory synaptic input mediated by GABAA receptors from at least two distinct sources. One, probably originating from the striatum, may be depressed via presynaptic 5-HT1B and GABAB receptors. The second is likely to arise from axon collaterals of SNr neurons themselves and is facilitated by an increase in firing via postsynaptic, somatodendritic 5-HT2C receptor activation, but it is depressed by GABAB receptor activation. Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectively, but excitation may be limited by GABA released from axon collaterals.