ELSC Seminar: Josh Goldberg

A lecture given by:

Josh Goldberg
Department of Medical Neurobiology
Institute of Medical Research Israel-Canada (IMRIC)
The Faculty of Medicine, The Hebrew University of Jerusalem


On the topic of:

"up-regulation of sodium currents boosts cortical input to striatal cholinergic interneurons in mouse models of Huntington's disease"

Thursday, January 9, 2014


Abstract:

In Huntington's disease (HD) -- a devastating autosomal-dominant neurodegenerative disease -- the striatum displays reduced cholinergic markers, despite the resiliency of cholinergic interneurons (ChIs) -- the source of striatal acetylcholine -- to the neurodegeneration that decimates striatal projection neurons. Autonomous spiking of ChIs is unchanged in transgenic HD mice, suggesting a functional deficit in extrinsically driven activity. Using two transgenic mouse models of HD, we show that ChI responses to cortical input are boosted by a post-synaptic up-regulation of the persistent sodium current. This boosting is replicated by in wild-type mice by diminished activation of group I metabotropic glutamate receptors (mGluRs). Activation of group I mGluRs in HD mice counters the boosting. We propose that the recently described loss of thalamic synapses in striatum, reduces group I mGluR activation in ChIs which promotes boosting of cortical inputs. The augmentation of cortical inputs may function to compensate for the lost thalamic glutamatergic drive.