Direct Action of two major Antidepressants on a Specific Inhibitory Circuit of the Hippocampus
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1
European Brain Research Institute, Italy
Hippocampal inhibitory synapses innervating the perisomatic region of principal pyramidal neurons originate from different basket cell subtypes. Specific properties of these inhibitory synapses differently control hippocampal functions. Fast-spiking (FS) interneurons exert a tight temporal control of network activities, and support feed-forward inhibition. Conversely, cannabinoid receptor 1(CB1R)-positive basket cells generate feedback inhibition and were proposed to control mood and emotional states. Alterations of GABA release from specific soma-targeting interneurons might thus result in mood disorders. Here we studied the effects on inhibitory neurotransmission onto CA1 hippocampal pyramidal cells of two major antidepressants: imipramine, a tricyclic antidepressant and fluoxetine, a selective serotonin reuptake inhibitor. Application of either drug strongly reduced evoked inhibitory postsynaptic currents and increased the excitation-inhibition ratio on pyramidal neurons in acute slices from rodents. These effects had a presynaptic origin and were independent of the known actions of these drugs on aminergic reuptake systems. Interestingly, antidepressants affected selective inhibitory circuits, as both drugs reduced feed-forward inhibition, leaving the CB1R-sensitive feedback loop unaffected. Pair recordings of unitary synaptic responses between identified basket cells and pyramidal neurons showed that these antidepressants reduced inhibition originating from FS cells, but not from CB1R+ interneurons. Despite their widespread use in clinic, the precise mechanism of action of antidepressant drugs is still debated. Our results demonstrate that hippocampal inhibitory circuits are selectively and directly affected by two major antidepressants and suggest a new mechanism of action of these drugs in the central nervous system. We are currently testing how this selective suppression of feed-forward inhibition affects network hippocampal activities.
Conference:
EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010.
Presentation Type:
Poster Presentation
Topic:
Posters
Citation:
Bacci
A,
Mendez
P and
Pazienti
A
(2010). Direct Action of two major Antidepressants on a Specific Inhibitory Circuit of the Hippocampus.
Conference Abstract:
EMBO workshop: Gaba Signalling and Brain Networks .
doi: 10.3389/conf.fnins.2010.15.00016
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Received:
24 Jun 2010;
Published Online:
24 Jun 2010.
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Correspondence:
P. Mendez, European Brain Research Institute, Rome, Italy, p.mendez@ebri.it