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Altered profile of basket cell afferent synapses in hyper‐excitable dentate gyrus revealed by optogenetic and two‐pathway stimulations
Author(s) -
Ledri Marco,
Nikitidou Litsa,
Erdelyi Ferenc,
Szabo Gabor,
Kirik Deniz,
Deisseroth Karl,
Kokaia Merab
Publication year - 2012
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2012.08080.x
Subject(s) - dentate gyrus , neuroscience , excitatory postsynaptic potential , inhibitory postsynaptic potential , hippocampal formation , optogenetics , hippocampus , gabaergic , chemistry , cholecystokinin , biology , receptor , biochemistry
Cholecystokinin (CCK‐) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine‐tuning devices of hippocampal gamma‐frequency (30–90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK‐basket cells may play an important role in regulation of hyper‐excitability and seizures in the hippocampus. In normal conditions, the endogenous excitability regulator neuropeptide Y (NPY) has been shown to modulate afferent inputs onto dentate gyrus CCK‐basket cells, providing a possible novel mechanism for excitability control in the hippocampus. Using GAD65‐GFP mice for CCK‐basket cell identification, and whole‐cell patch‐clamp recordings, we explored whether the effect of NPY on afferent synapses to CCK‐basket cells is modified in the hyper‐excitable dentate gyrus. To induce a hyper‐excitable state, recurrent seizures were evoked by electrical stimulation of the hippocampus using the well‐characterized rapid kindling protocol. The frequency of spontaneous and miniature excitatory and inhibitory post‐synaptic currents recorded in CCK‐basket cells was decreased by NPY. The excitatory post‐synaptic currents evoked in CCK‐basket cells by optogenetic activation of principal neurons were also decreased in amplitude. Interestingly, we observed an increased proportion of spontaneous inhibitory post‐synaptic currents with slower rise times, indicating that NPY may inhibit gamma aminobutyric acid release preferentially in peri‐somatic synapses. These findings indicate that increased levels and release of NPY observed after seizures can modulate afferent inputs to CCK‐basket cells, and therefore alter their impact on the oscillatory network activity and excitability in the hippocampus.