Primary motor cortex of the parkinsonian monkey: altered neuronal responses to muscle stretch

Abstract

Exaggeration of the long-latency stretch reflex (LLSR) is a characteristic neurophysiologic feature of Parkinson's disease (PD) that contributes to parkinsonian rigidity. To explore one frequently-hypothesized mechanism, we studied the effects of fast muscle stretches on neuronal activity in the macaque primary motor cortex (M1) before and after the induction of parkinsonism by unilateral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We compared results from the general population of M1 neurons and two antidromically-identified subpopulations: distant-projecting pyramidal-tract type neurons (PTNs) and intra-telecenphalic-type corticostriatal neurons (CSNs). Rapid rotations of elbow or wrist joints evoked short-latency responses in 62% of arm-related M1 neurons. As in PD, the late electromyographic responses that constitute the LLSR were enhanced following MPTP. This was accompanied by a shortening of M1 neuronal response latencies and a degradation of directional selectivity, but surprisingly, no increase in single unit response magnitudes. The results suggest that parkinsonism alters the timing and specificity of M1 responses to muscle stretch. Observation of an exaggerated LLSR with no change in the magnitude of proprioceptive responses in M1 is consistent with the idea that the increase in LLSR gain that contributes to parkinsonian rigidity is localized to the spinal cord.

Motor learning in animal models of Parkinson's disease: Aberrant synaptic plasticity in the motor cortex

“…Given that pathological activity in the motor cortex may translate into the motor signs observed in PD, the synaptic adaptations and neuronal activities involved in the PD motor cortex have begun to attract more and more attention in recent years . The study detailed above in which researchers examined the remodeling of the motor cortex neural circuits in a PD model through combining in vivo imaging of spine dynamics, electrophysiological analyses of synaptic functional plasticity, and behavioral investigation, provides evidence for abnormal remodeling in PD motor cortex, and allows us to better understand the mechanisms underlying motor skill learning and memory deficits in PD .…”

Primary motor cortex and fast feedback responses to mechanical perturbations: a primer on what we know now and some suggestions on what we should find out next

“…Similarly, posterior parietal cortex is involved in attentional mechanisms and motor control (Andersen and Buneo, 2002 ), receives inputs from somatosensory cortex and projects to the frontal cortex including M1 (Petrides and Pandya, 1984 ). Diseases of the basal ganglia typically lead to markedly exaggerated long-latency stretch responses (Tatton and Lee, 1975 ; Rothwell et al, 1983 ), which may reflect changes in the transcortical pathway (DeLong and Wichmann, 2007 ), though recent studies with Parkinsonian monkeys suggest that such effects are more complicated than mere changes in the sensitivity of M1 neurons to sensory input (Pasquereau and Turner, 2013 ). And recently, a compelling argument has been made that startle-like brain stem processes contribute to the long-latency stretch response in various contexts (Shemmell et al, 2010 ) and, indeed, neurons in the reticular formation that project to the distal arm muscles also respond to mechanical perturbations at such short latencies that they likely contribute to muscle activity in the long-latency epoch (Soteropoulos et al, 2012 ).…”

The Phenomenology of Parkinson's Disease

“…Recent studies have focused on modifying the standard clinical evaluation for PD by excluding rigidity rather than seeking a proxy measure to substitute or calculate for rigidity. 40 The etiology of rigidity in PD is complex; the clinical impression of rigidity has been shown to correlate with long latency reflex characteristics, 41 and contributions have been proposed not only from failures to relax, abnormalities in stretch reflexes, and the mechanical properties of muscle, 42,43 but also from potential contributions of abnormal basal ganglia activity on spinal reflexes. 41,44 Although an examiner is necessary to appreciate rigidity directly, its effects can be seen during gait, in which a reduction in the pendular movement of the arms (arm swing) throughout the phases of locomotion in patients with PD is observed.…”