Serotonergic modulation of neurotransmission in the rat basolateral amygdala.
Whole cell patch-clamp recordings were obtained from projection neurons and interneurons of the rat basolateral amygdala (BLA) to understand local network interactions in morphologically identified neurons and their modulation by serotonin. Projection neurons and interneurons were characterized morphologically and electrophysiologically according to their intrinsic membrane properties and synaptic characteristics. Synaptic activity in projection neurons was dominated by spontaneous inhibitory postsynaptic currents (IPSCs) that were multiphasic, reached 181 +/- 38 pA in amplitude, lasted 296 +/- 27 mS, and were blocked by the GABAA receptor antagonist, bicuculline methiodide (30 microM). In interneurons, spontaneous synaptic activity was characterized by a burst-firing discharge patterns (200 +/- 40 Hz) that correlated with the occurrence of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive, high-amplitude (260 +/- 42 pA), long-duration (139 +/- 19 mS) inward excitatory postsynaptic currents (EPSCs). The interevent interval of 831 +/- 344 mS for compound inhibitory postsynaptic potentials (IPSPs), and 916 +/- 270 mS for EPSC bursts, suggested that spontaneous IPSP/Cs in projection neurons are driven by burst of action potentials in interneurons. Hence, BLA interneurons may regulate the excitability of projection neurons and thus determine the degree of synchrony within ensembles of BLA neurons. In interneurons 5-hydroxytryptamine oxalate (5-HT) evoked a direct, dose-dependent, membrane depolarization mediated by a 45 +/- 6.9 pA inward current, which had a reversal potential of -90 mV. The effect of 5-HT was mimicked by the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), but not by the 5-HT1A receptor agonist, (+/-) 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), or the 5-HT1B agonist, CGS 12066A. In projection neurons, 5-HT evoked an indirect membrane hyperpolarization ( approximately 2 mV) that was associated with a 75 +/- 42 pA outward current and had a reversal potential of -70 mV. The response was independent of 5-HT concentration, blocked by TTX, mimicked by alpha-methyl-5-HT but not by 8-OH-DPAT. In interneurons, 5-HT reduced the amplitude of the evoked EPSC and in the presence of TTX (0.6 microM) reduced the frequency of miniature EPSCs but not their quantal content. In projection neurons, 5-HT also caused a dose-dependent reduction in the amplitude of stimulus evoked EPSCs and IPSCs. These results suggest that acute serotonin release would directly activate GABAergic interneurons of the BLA, via an activation of 5-HT2 receptors, and increase the frequency of inhibitory synaptic events in projection neurons. Chronic serotonin release, or high levels of serotonin, would reduce the excitatory drive onto interneurons and may act as a feedback mechanism to prevent excess inhibition within the nucleus.
Rainnie
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Harvard Medical School and Brockton Veterans Affairs Medical Center, Department of Psychiatry, Neuroscience Laboratory 151C, Brockton, Massachusetts 02301, USA.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D058787:GABA-A Receptor Antagonists; D011810:Quinoxalines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C052561:CGS 12066B; C042390:alpha-methylserotonin; D012701:Serotonin; C017069:bicuculline methiodide; D013779:Tetrodotoxin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001640:Bicuculline