Spontaneous neuronal activity in the motor thalamus of dopamine-intact
and Parkinsonian rats in vivo
Kouichi C. Nakamura, Andrew Sharott, Nicolas Mallet, Peter J. Magill
Medical Research Council Anatomical Neuropharmacology Unit, University
of Oxford, Oxford, UK
Supported by/grant awarding body
Medical Research Council UK, Parkinson’s UK, Human Frontier Science
Program Organisation
Abstract
Movement difficulties in Parkinson’s disease are accompanied by inappropriately
synchronized beta oscillations (13-30Hz) in the cortex and basal ganglia.
Because motor thalamus is a major gateway for information flow from basal
ganglia to cortex, it is imperative to define how dopamine loss disturbs motor
thalamic activity in order to understand how these abnormal brain rhythms are
generated. Rat motor thalamus is comprised of basal ganglia-recipient and
cerebellar-recipient zones, which can be delineated with GAD67 and VGLUT2
immunoreactivities. These zones are bombarded by GABAergic inputs from
basal ganglia and glutamatergic inputs from cerebellar nuclei, respectively. We
used electrophysiological recordings of thalamic neurons in anaesthetised rats to
address whether neurons in different zones of motor thalamus exhibit different
activities in dopamine-intact and Parkinsonian rats. We recorded the
spontaneous activity of identified motor thalamic neurons and verified their
locations with immunolabeling for GAD67 and VGLUT2. We found that the firing
rates and patterns of neurons in both zones were closely dependent on brain
state. However, irrespective of brain state, the mean firing rates of neurons in the
two zones were similar. Statistical analyses only found differences in patterns of
low-threshold spike bursts. Thus, the contrasting input organizations of the two
zones of motor thalamus are not reflected in firing rates but by subtle differences
in firing patterns at rest. Using the 6-hydroxydopamine-lesioned rat model of
Parkinson’s disease, we next explored how activity is disturbed in the two zones
of motor thalamus. Contrary to classic schemes of Parkinsonism, we found no
evidence of pathologically reduced firing rates in either zone of motor thalamus of
lesioned rats. However, many neurons in the basal ganglia-recipient zone, but
not the cerebellar-recipient zone, exhibited abnormal beta oscillations. We
conclude that movement difficulties in Parkinsonism may be related more closely
to abnormal firing patterns than altered firing rates.