Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.
(2012) In European Journal of Neuroscience 36(1). p.1971-1983- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2519314
- author
- Ledri, Marco LU ; Nikitidou, Litsa LU ; Erdelyi, Ferenc ; Szabo, Gabor ; Kirik, Deniz LU ; Deisseroth, Karl and Kokaia, Merab LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Neuroscience
- volume
- 36
- issue
- 1
- pages
- 1971 - 1983
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000305903000003
- pmid:22512307
- scopus:84863210748
- ISSN
- 1460-9568
- DOI
- 10.1111/j.1460-9568.2012.08080.x
- language
- English
- LU publication?
- yes
- id
- 6934d266-d947-4148-bc01-5b89a570c679 (old id 2519314)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22512307?dopt=Abstract
- date added to LUP
- 2016-04-01 10:29:30
- date last changed
- 2023-09-28 06:46:09
@article{6934d266-d947-4148-bc01-5b89a570c679, abstract = {{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.}}, author = {{Ledri, Marco and Nikitidou, Litsa and Erdelyi, Ferenc and Szabo, Gabor and Kirik, Deniz and Deisseroth, Karl and Kokaia, Merab}}, issn = {{1460-9568}}, language = {{eng}}, number = {{1}}, pages = {{1971--1983}}, publisher = {{Wiley-Blackwell}}, series = {{European Journal of Neuroscience}}, title = {{Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.}}, url = {{http://dx.doi.org/10.1111/j.1460-9568.2012.08080.x}}, doi = {{10.1111/j.1460-9568.2012.08080.x}}, volume = {{36}}, year = {{2012}}, }