TY - JOUR
T1 - Regulation of interneuron excitability by gap junction coupling with principal cells
AU - Apostolides, Pierre F.
AU - Trussell, Laurence O.
N1 - Funding Information:
We thank M. Roberts and S. Kuo for preliminary observations that led us to search for electrical coupling in the DCN; M. Bateschell and R. Larisch for help with mouse colony management and genotyping; C. Borges-Merjane (Vollum Institute/Oregon Hearing Research Center) for initially genotyping the Thy1-ChR2 mice and providing the cerebellum slices used in Supplementary Figure 2; H.-W. Lu for writing the macros used to analyze the calcium imaging data; S. Foster for performing the auditory brainstem response measurements; and K. Bender, W. Giardino and N. Sawtell for critical comments on the manuscript. Funding was provided by US National Institutes of Health grants R01DC004450 to L.O.T., F31DC012222 to P.F.A. and P30 DC005983 to the Oregon Hearing Research Center.
PY - 2013
Y1 - 2013
N2 - Electrical coupling of inhibitory interneurons can synchronize activity across multiple neurons, thereby enhancing the reliability of inhibition onto principal cell targets. It is unclear whether downstream activity in principal cells controls the excitability of such inhibitory networks. Using paired patch-clamp recordings, we show that excitatory projection neurons (fusiform cells) and inhibitory stellate interneurons of the dorsal cochlear nucleus form an electrically coupled network through gap junctions containing connexin36 (Cxc36, also called Gjd2). Remarkably, stellate cells were more strongly coupled to fusiform cells than to other stellate cells. This heterologous coupling was functionally asymmetric, biasing electrical transmission from the principal cell to the interneuron. Optogenetically activated populations of fusiform cells reliably enhanced interneuron excitability and generated GABAergic inhibition onto the postsynaptic targets of stellate cells, whereas deep afterhyperpolarizations following fusiform cell spike trains potently inhibited stellate cells over several hundred milliseconds. Thus, the excitability of an interneuron network is bidirectionally controlled by distinct epochs of activity in principal cells.
AB - Electrical coupling of inhibitory interneurons can synchronize activity across multiple neurons, thereby enhancing the reliability of inhibition onto principal cell targets. It is unclear whether downstream activity in principal cells controls the excitability of such inhibitory networks. Using paired patch-clamp recordings, we show that excitatory projection neurons (fusiform cells) and inhibitory stellate interneurons of the dorsal cochlear nucleus form an electrically coupled network through gap junctions containing connexin36 (Cxc36, also called Gjd2). Remarkably, stellate cells were more strongly coupled to fusiform cells than to other stellate cells. This heterologous coupling was functionally asymmetric, biasing electrical transmission from the principal cell to the interneuron. Optogenetically activated populations of fusiform cells reliably enhanced interneuron excitability and generated GABAergic inhibition onto the postsynaptic targets of stellate cells, whereas deep afterhyperpolarizations following fusiform cell spike trains potently inhibited stellate cells over several hundred milliseconds. Thus, the excitability of an interneuron network is bidirectionally controlled by distinct epochs of activity in principal cells.
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U2 - 10.1038/nn.3569
DO - 10.1038/nn.3569
M3 - Article
C2 - 24185427
AN - SCOPUS:84888330573
SN - 1097-6256
VL - 16
SP - 1764
EP - 1772
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 12
ER -