Richard A. Warren

Glutamate activation of cat thalamic reticular nucleus: effects on response properties of ventroposterior neurons

The thalamic reticular nucleus (RTN) exerts an inhibitory influence upon the dorsal thalamus. During wakefulness and arousal, RTN neurons fire tonically, whereas during slow-wave sleep they fire rhythmic high frequency bursts. The effects produced by RTN inhibition upon the activity of dorsal thalamic neurons will therefore vary in relation to the firing mode of the RTN neurons. In the present study, we compared the effects of oscillating RTN neurons and of RTN neurons tonically activated with glutamate on the response profiles of single units reacting to controlled cutaneous stimulation in cat ventroposterior lateral thalamic nucleus (VPL). Experiments were performed under light barbiturate anesthesia and prior to the glutamate activation of the RTN, both RTN and VPL neurons showed spontaneous bursting patterns of activity consistent with the oscillatory mode. Typically, a cutaneous stimulus evoked a short latency excitatory response in VPL followed by a period of complete inhibition termed post-stimulus inhibition (PSI). In many neurons, the PSI was followed by a period of increased activity termed post-inhibitory excitation (PIE). Ejection of glutamate in the identified somatosensory division of the RTN shifted the oscillatory firing of its neurons to a high tonic mode and usually resulted in a decrease in VPL neuronal activity. Significant variations were observed in the occurrence and the magnitude of the effects among the different components of neuronal activity examined. Tonic activation of the RTN resulted in a significant reduction of ON- and OFF-PIEs in 81% of cases (30/37) and of spontaneous activity in 67% (22/ 33). In contrast, the response to a cutaneous stimulus was decreased in only 29% of cases (17/59) and was significantly increased in 24% (14/59). Tonic activation of the RTN by glutamate resulted in little change in the firing pattern of VPL neurons, and both short and long spike intervals were affected in a similar proportion. We conclude that the components of VPL neuronal activity most affected by switching RTN neurons from the oscillatory to the tonic mode are those normally dependent upon RTN neuronal oscillation. The present results also suggest that lowering background activity, such as occurs during the transition from sleep to wakefulness, is a factor leading to increase in the responsiveness of dorsal thalamic neurons.

Cholinergic Modulation of Synaptic Plasticity in Sensory Neocortex

Activity-dependent synaptic plasticity occurs in neocortex devoted to each sensory system at all postnatal ages. The process is crucial for the refinement of topographic cortical representations and the development of stimulus selectivity in the neonate, and although the plasticity is more subtle in the adult cortex, it probably forms the basis of dynamic changes in sensory representations and may account for some forms of memory. A question of central importance is whether the fundamental mechanisms of neuronal plasticity are the same at different ages and in different cortical areas.

Population analysis of single neurons in cat somatosensory cortex.

Single neurons in the somatosensory cortex are divisible into a population with receptive fields and a population without receptive fields. These two populations display different laminar distributions, and their respective functions are unknown. We compared other physiological characteristics of these two neuronal populations in an attempt to understand why some neurons lack a receptive field. Only 23% of 465 neurons isolated in the somatosensory cortex of halothane-anesthetized cats displayed a cutaneous receptive field. The iontophoretic administration of glutamate uncovered input from the periphery in another 34% of the sample, leaving 43% of the neurons without evidence of peripheral input under these experimental conditions. Neurons with a receptive field were spontaneously active much more often than neurons lacking peripheral inputs, and their rates of discharge were higher. No differences were found between neurons having a receptive field uncovered with glutamate and those unaffected by glutamate. In all classes of neurons, those cells with spontaneous activity were excited by smaller amounts of glutamate than were silent neurons, but sensitivity to glutamate was not correlated with the presence or absence of a receptive field. We infer that some classes of somatosensory cortical neurons receive strong thalamocortical inputs, whereas others have only relatively weak or no thalamocortical connections. In other experiments we have shown also that those neurons lacking a receptive field and/or spontaneous activity were more likely to be plastic than those with stronger inputs (see Warren and Dykes, 1993a,b), suggesting that neurons having weaker afferent inputs can be more readily modified under certain circumstances.

Neuromodulatory Substances, Somatosensory Cortical Neuronal Responsiveness and Long-term Changes in Neuronal Excitability

Models of the somatosensory system require that the patterns of neuronal activity which relay sensory information along systems of neurons between the skin surface and somatosensory cortex reproduce the spatial and temporal characteristics of the cutaneous message with a fidelity sufficient to account for the sensory discriminations which that information elicits (Mountcastle, 1975). Furthermore these models presume that identical stimuli produce nearly identical spatiotemporal patterns and that any differences among the neural patterns evoked by identical stimuli determine the limits of an the animal’s ability to detect or discriminate among those stimuli. The reproducibility of the behavioral data and of their neural correlates imply that the functional characteristics of neurons in the somatosensory pathway are highly reproducible over time and that faithful central representations of sensory events are dependent upon their reproducibility.