Dysregulated information processing by medium spiny neurons in striatum of freely behaving mouse models of Huntington's disease.
Huntington's disease (HD) is an autosomal dominant condition that compromises behavioral output. Dysfunction of medium spiny neurons (MSNs), which are the sole output system of the striatum, is thought to underlie HD pathophysiology. What is not known is how HD alters MSN information processing during behavior, which likely drives the HD behavioral phenotype. We recorded from populations of MSNs in two freely behaving and symptomatic HD mouse models: R6/2 transgenics are based on a C57BL/6J*CBA/J background and show robust behavioral symptoms, whereas knock-in (KI) mice have a 129sv background and express relatively mild behavioral signs. At the single-unit level, we found that the MSN firing rate was elevated in R6/2 but not in KI mice compared with their respective wild-type (WT) controls. In contrast, burst activity, which corresponds to periods of high-frequency firing, was altered in both HD models compared with WT. At the population level, we found that correlated firing between pairs of MSNs was a prominent feature in WT that was reduced in both HD models. Similarly, coincident bursts, which are bursts between pairs of neurons that overlap in time and occur more often in pairs of MSNs that exhibit correlated firing, were decreased in HD mice. Our results indicate an important role in both bursting and correlated burst firing for information processing in MSNs. Dysregulation of this processing scheme, moreover, is a key component of HD pathophysiology regardless of the severity of HD symptoms, genetic construct, and background strain of the mouse models.
Miller
Benjamin R
BR
Program in Neuroscience, Department of Psychological and Brain Sciences, Indiana University, 1101 East 10th St., Bloomington, IN 47405, USA.
Walker
Adam G
AG
Shah
Anand S
AS
Barton
Scott J
SJ
Rebec
George V
GV
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004567:Electrodes, Implanted; D004594:Electrophysiology; D005106:Exploratory Behavior / Q000502:physiology; D005838:Genotype; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008606:Mental Processes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017072:Neostriatum / Q000166:cytology / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid