Document Detail


Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.
MedLine Citation:
PMID:  22512307     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Marco Ledri; Litsa Nikitidou; Ferenc Erdelyi; Gabor Szabo; Deniz Kirik; Karl Deisseroth; Merab Kokaia
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-18
Journal Detail:
Title:  The European journal of neuroscience     Volume:  -     ISSN:  1460-9568     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Affiliation:
Experimental Epilepsy Group, Division of Neurology, Wallenberg Neuroscience Centre, Lund University Hospital, Lund, Sweden Department of Gene Technology and Developmental Neurobiology, Institute for Experimental Medicine, Budapest, Hungary Brain Repair and Imaging in Neural Systems (BRAINS) Unit, Department of Experimental Medical Sciences, Lund University Hospital, Lund, Sweden Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
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