Brigitte Lavoie

Input-output properties and gain changes in the human corticospinal pathway.

Abstract Experiments were done to determine the form of the input-output relation (i.e. stimulus intensity vs response amplitude) of the corticospinal pathway of the first dorsal interosseous and the tibialis anterior, respectively. Our purpose was to determine from these quantitative relations which input-output parameters would be useful measures in studies dealing with motor cortical task dependence. The motor cortex was excited by focal transcranial magnetic stimuli and the evoked motor response were recorded with surface electromyographic electrodes. In some experiments the discharge probability of single motor units in response to magnetic stimuli of increasing intensity was determined from intramuscular recordings. For both muscles the form of the input-output relation was sigmoidal. The steepness of the relation increased, up to 4–7 times the value at rest, with increasing tonic background activity. The threshold decreased, but only slightly, with increasing tonic background activity. The minimum value of the threshold was reached at activation levels of about 10–20% of the maximum tonic effort, whereas the steepness of the relation reached its maximum at higher activation levels, typically about 30–40% of the maximum tonic effort. These observations imply that these two input-output parameters of the corticospinal pathway – one reflecting the bias level (threshold) and the other the gain (slope) – are determined by different neural mechanisms. The plateau level of the sigmoidal input-output relation was not influenced by the background activation level, except that in some subjects (4/9) it could not be reached when no background motor activity was present. This was probably due, for the most part, to limitation of the maximum stimulator output. Additionally, this finding may reflect a change in the intrinsic excitability of the motor cortex in going from rest to activity, or that convergent inputs from different descending and afferent systems are required for maximal activation of motoneuron pools. Thus, the threshold, steepness and plateau level characterize the input-output parameters of the human corticospinal pathway for a given level of motor activity. In contrast to the nonlinear input-output relation of the corticospinal pathway as whole, which includes the motoneuron pool and any spinal interneuronal relays, the discharge probability of all single motor units was a linearly increasing function of the stimulus strength (r≥0.9, P<0.01). Thus, the sigmoidal input-output relation of the corticospinal pathway, as a whole, is not due to the input-output properties of single motoneurons. The possible neural mechanisms which underlie the shape and parameters of the input-output relation as well as the methodological implications of the results are considered.

Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys

In cynomolgus monkeys, midbrain neurons immunoreactive (IR) for the calcium-binding protein calbindin D-28k (CaBP) occur principally in the dorsal tier of substantia nigra pars compacta (SNc) and in the ventral tegmental area (VTA), and most of these neurons co-express tyrosine hydroxylase (TH). In monkeys rendered parkinsonian (PD) after MPTP injections, CaBP-IR neurons are much less severely affected than TH-IR neurons in SNc and in VTA, and most spared neurons in SNc/VTA display both CaBP and TH immunoreactivity. These results reveal that, in contrast to the situation in other neurodegenerative diseases, CaBP may be used as a marker for a specific neuronal population that is less prone to degeneration in Parkinsons disease.

Chemical anatomy of primate basal ganglia

This paper provides an overview of the anatomical and functional organization of the most prominent chemospecific neuronal systems that compose the basal ganglia in primates. Emphasis is placed on the heterogeneity and diversity of small-molecule transmitters, neuroactive peptides and proteins used by basal ganglia neurons. Dopaminergic, serotoninergic and cholinergic neuronal systems are shown to comprise multiple subsystems organized according to highly specific patterns. These subsystems differentially regulate gene expression of several neuroactive peptides, including tachykinins, enkephalins, dynorphin, somatostatin, and neuropeptide Y, that are used by distinct subsets of basal ganglia neurons. Glutamatergic excitatory inputs establish distinct functional territories within the basal ganglia, and neurons in each of these territories act upon other brain neuronal systems through a GABAergic disinhibitory output mechanism. A striking complementary pattern of distribution of the calcium-binding proteins parvalbumin and calbindin D-28k is noted in all basal ganglia components. The limbic system-associated membrane protein (LAMP) is confined chiefly to basal ganglia sectors that are anatomically and functionally related to limbic system structures; these may serve as functional interfaces between the basal ganglia and the limbic system. The functional status of the various basal ganglia chemospecific systems in neurodegenerative diseases, such as Parkinsons disease and Huntingtons chorea, is examined. It is concluded that these multiple transmitter-related systems cannot be analyzed separately as they form highly complex and interactive neuronal networks. These complexities should be taken into account to reach a better understanding of the functions of primate basal ganglia in health and disease.

Evidence for a distinct nigropallidal dopaminergic projection in the squirrel monkey

Injections of the retrograde fluorescent tracer fast blue in the striatum (STR) and nuclear yellow in the internal segment of the globus pallidus (GPi) in the squirrel monkey (Saimiri sciureus) revealed a nigropallidal projection whose cellular origin was largely distinct from that of the nigrostriatal pathway. Neurons containing the tracer injected in GPi were scattered throughout the substantia nigra-ventral tegmental area complex where they formed approximately 20-25% of the total number of retrogradely labeled cells. Only about 5-10% of all positive neurons were double-labeled after STR-GPi injections. In experiments combining the use of the fluorescent tracer propidium iodide with immunofluorescence, the majority of neurons projecting to GPi displayed tyrosine hydroxylase immunoreactivity. Hence, in addition to their important role at striatal level, midbrain dopaminergic neurons may influence directly the output neurons of the basal ganglia at pallidal level in primates.

Neural mechanisms involved in the functional linking of motor cortical points.

We sought to understand the basic neural processes involved in the functional linking of motor cortical points. We asked which of the two basic neural mechanisms, excitation or inhibition, is required to functionally link motor cortical points. In the ketamineanaesthetized cat, a microstimulation electrode was positioned at a point (control point) that was identified by the following three characteristics of the EMG responses: the muscle(s) activated at threshold, any additional muscles recruited by supra-threshold stimulation, and their relative latency. A second distinct point (test point) producing activation of a muscle at a different joint was then identified. At this test cortical point the GABAA receptor antagonist bicuculline was ejected iontophoretically, while stimulating the control point near threshold. A combined response was elicited consisting of the response normally elicited at the control point plus that elicited at the test point. Thus, an artificial muscle synergy was produced following disinhibition of the test point. This was never the case when glutamate was ejected at the test point, even when supra-threshold stimuli were used at the control point. Therefore, simply increasing the excitability of a cortical point was not sufficient to release the muscle(s) represented at that point into a muscle synergy. Kynurenate, a broadly acting excitatory amino acid receptor antagonist, ejected at the bicuculline point reversed the effect of bicuculline. This shows that the release phenomenon was mediated synaptically and was not due to spread of the stimulating current. We suggest that release from inhibition may be one of the neural mechanisms involved in functionally linking motor cortical points. This functional linking may be part of the ensemble of motor cortical mechanisms involved in recruitment of muscle synergies.

The interaction among age, thermal acclimation and growth rate in determining muscle metabolic capacities and tissue masses in the threespine stickleback, Gasterosteus aculeatus

Thermal acclimation may directly modify muscle metabolic capacities, or may modify them indirectly via effects upon physiological processes such as growth, reproduction or senescence. To evaluate these interacting effects, we examined the influence of thermal acclimation and acclimatization upon muscle metabolic capacities and tissue masses in 1 + stickleback, Gasterosteus aculeatus, in which confounding interactions between temperature and senescense should be absent. Furthermore, we examined the influence of thermal acclimation upon individual growth rate, muscle enzyme levels and tissue masses in 2 + stickleback sampled at the beginning of their final reproductive season. For 1 + stickleback, cold acclimation more than doubles mitochondrial enzyme levels in the axial muscle. Thermal acclimation did not change the condition of 1 + stickleback at feeding levels which could not maintain the condition of 2+ stickleback. Compensatory metabolic responses to temperature were not apparent in field acclimatized 1 + stickleback. The growth rate of 2 + stickleback was markedly affected by temperature: warm-acclimated fish generally lost mass even at very high levels of feeding (up to 78 enchytraid worms per day) while cold-acclimated fish gained mass. This suggests that warm temperatures accelerate the senescence of 2 + stickleback. Generally, muscle enzyme activities increased with growth rate. In axial muscle, the relationships between CS activity and growth rate differed with acclimation temperature. Independent of the influence of growth rate, CS activities were consistently higher in cold- than warm-acclimated 2 + stickleback, suggesting compensatory increases of CS activity with cold acclimation.

The Pallidum as a Dual Structure in Primates

This paper reviews some of our most recent findings on the organization of the afferent and efferent connections of the globus pallidus (GP) in the squirrel monkey (Saimiri sciureus). Its main purpose is to demonstrate that even though all pallidal neurons express the same phenotype in terms of both morphology and chemospecificity, the analysis of afferent and efferent connections of GP reveals that this major component of the basal ganglia is in fact a dual entity in primates.

Studies of Presynaptic Inhibition in the Stretch Reflex Pathway of the Human and the Cat

Presynaptic inhibition of muscle afferent terminals in the spinal cord, including perhaps those of Ib afferents, is a potential and direct mechanism for control of the stretch reflex parameters. Eccles (1964), in reviewing the extensive studies of his group on the cellular basis and network organisation of presynaptic inhibition in the spinal cord, expressed the view that this form of inhibition was in fact more potent than postsynaptic inhibition. Despite this, the functional role of presynaptic inhibition in motor control has, only recently, begun to be studied. Matthews (1972) commented that presynaptic inhibitory mechanisms have not, in general, been incorporated into ideas of how the spinal cord controls movements because of a lack of quantitative measures of its effects. In this chapter we describe the results of two experimental studies bearing on the functional role of presynaptic inhibition during walking in humans and on the biomechanical consequences of presynaptic inhibition of the stretch reflex (s.r.).