Autism Related Neuroligin-4 Knockout Impairs Intracortical Processing but not Sensory Inputs in Mouse Barrel Cortex
| Autor: | Jenq-Wei Yang, Heiko J. Luhmann, Matthieu Hammer, Dilja Krueger-Burg, Sergei Kirischuk, Petr Unichenko, Werner Kilb, Nils Brose, Sergei N. Kolbaev |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Adhesion Molecules Neuronal Cognitive Neuroscience Hippocampus Neocortex Neuroligin Sensory system In Vitro Techniques Neurotransmission Mice 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic 0302 clinical medicine Animals Evoked Potentials Synapse organization Mice Knockout Neurons Afferent Pathways Neurotransmitter Agents Chemistry Barrel cortex Electric Stimulation Voltage-Sensitive Dye Imaging 030104 developmental biology Animals Newborn Vibrissae Excitatory postsynaptic potential Nerve Net Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cerebral Cortex. 28:2873-2886 |
| ISSN: | 1460-2199 1047-3211 |
| DOI: | 10.1093/cercor/bhx165 |
| Popis: | Neuroligin-4 (Nlgn4) is a cell adhesion protein that regulates synapse organization and function. Mutations in human NLGN4 are among the causes of autism spectrum disorders. In mouse, Nlgn4 knockout (KO) perturbs GABAergic synaptic transmission and oscillatory activity in hippocampus, and causes social interaction deficits. The complex profile of cellular and circuit changes that are caused by Nlgn4-KO is still only partly understood. Using Nlgn4-KO mice, we found that Nlgn4-KO increases the power in the alpha frequency band of spontaneous network activity in the barrel cortex under urethane anesthesia in vivo. Nlgn4-KO did not affect single-whisker-induced local field potentials, but suppressed the late evoked multiunit activity in vivo. Although Nlgn4-KO did not affect evoked EPSCs in layer 4 (L4) spiny stellate cells in acute thalamocortical slices elicited by electrical stimulation of thalamocortical inputs, it caused a lower frequency of both miniature (m) IPSCs and mEPSCs, and a decrease in the number of readily releasable vesicles at GABAergic and glutamatergic connections, weakening both excitatory and inhibitory transmission. However, Nlgn4 deficit strongly suppresses glutamatergic activity, shifting the excitation-inhibition balance to inhibition. We conclude that Nlgn4-KO does not influence the incoming whisker-mediated sensory information to the barrel cortex, but modifies intracortical information processing. |
| Databáze: | OpenAIRE |
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