Abnormal burst patterns of single neurons recorded in the substantia nigra reticulata of behaving 140 CAG Huntington's disease mice.

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes neurological pathology in the basal ganglia and related circuitry. A key site of HD pathology is striatum, the principal basal ganglia input structure; striatal pathology likely changes basal ganglia output but no existing studies address this issue. In this report, we characterize single-neuron activity in the substantia nigra reticulata (SNr) of awake, freely behaving 140 CAG knock-in (KI) mice at 16-40 weeks. KI mice are a well characterized model of adult HD and are mildly symptomatic in this age range. As the primary basal ganglia output nucleus in rodents, the SNr receives direct innervation from striatum, as well as indirect influence via polysynaptic inputs. We analyzed 32 single neurons recorded from KI animals and 44 from wild-type (WT) controls. We found increased burst rates, without a concordant change in spike discharge rate, in KI animals relative to WTs. Furthermore, although metrics of burst structure, such as the inter-spike interval in bursts, do not differ between groups, burst rate increases with age in KI, but not WT, animals. Our findings suggest that altered basal ganglia output is a physiological feature of early HD pathology. Copyright Â