Thalamocortical Projections Are Significantly Impaired in the R6/2 Mouse Model of Huntington's Disease.

Area of Science:

• Neuroscience
• Neurodegenerative Diseases
• Electrophysiology

Background:

• Huntington's disease (HD) involves striatal neuron loss and cortical thinning.
• Early sensorimotor deficits in HD patients contrast with limited electrophysiological studies of thalamocortical circuits.
• Understanding thalamocortical circuit integrity is crucial for HD progression.

Purpose of the Study:

• To investigate the electrophysiological properties and connectivity of thalamocortical circuits in a mouse model of Huntington's disease.
• To assess functional changes in motor and somatosensory thalamocortical pathways in R6/2 mice.

Main Methods:

• Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL) and ventral posteromedial nucleus (VPM) thalamic neurons in ex vivo brain slices.
• Electrophysiological analysis of passive and active membrane properties, resting membrane potentials, and excitability.
• Optical activation of thalamic terminals to measure responses in cortical pyramidal neurons (CPNs) and analysis of excitatory quantal events.

Main Results:

• Thalamic neurons in R6/2 mice showed altered membrane properties (smaller capacitance, faster decay, increased resistance) compared to wild-type (WT).
• Symptomatic R6/2 mice exhibited increased excitability in both VAL and VPM thalamic nuclei.
• Reduced current responses and decreased frequency of excitatory quantal events were observed in thalamocortical pathways of symptomatic R6/2 mice.

Conclusions:

• Huntington's disease significantly impairs thalamocortical circuit connectivity in R6/2 mice.
• Reduced transmission of thalamocortical information is likely caused by impaired neurotransmitter release.
• These findings highlight functional deficits in sensory and motor processing relevant to HD progression.