Asaf Keller

Functional circuitry involved in the regulation of whisker movements

Neuroanatomical tract‐tracing methods were used to identify the oligosynaptic circuitry by which the whisker representation of the motor cortex (wMCx) influences the facial motoneurons that control whisking activity (wFMNs). Injections of the retrograde tracer cholera toxin subunit B into physiologically identified wFMNs in the lateral facial nucleus resulted in dense, bilateral labeling throughout the brainstem reticular formation and in the ambiguus nucleus as well as predominantly ipsilateral labeling in the paralemniscal, pedunculopontine tegmental, Kölliker‐Fuse, and parabrachial nuclei. In addition, neurons in the following midbrain regions projected to the wFMNs: superior colliculus, red nucleus, periaqueductal gray, mesencephalon, pons, and several nuclei involved in oculomotor behaviors. Injections of the anterograde tracer biotinylated dextran amine into the wMCx revealed direct projections to the brainstem reticular formation as well as multiple brainstem and midbrain structures shown to project to the wFMNs. Regions in which retrograde labeling and anterograde labeling overlap most extensively include the brainstem parvocellular, gigantocellular, intermediate, and medullary (dorsal and ventral) reticular formations; ambiguus nucleus; and midbrain superior colliculus and deep mesencephalic nucleus. Other regions that contain less dense regions of combined anterograde and retrograde labeling include the following nuclei: the interstitial nucleus of medial longitudinal fasciculus, the pontine reticular formation, and the lateral periaqueductal gray. Premotoneurons that receive dense inputs from the wMCx are likely to be important mediators of cortical regulation of whisker movements and may be a key component in a central pattern generator involved in the generation of rhythmic whisking activity. J. Comp. Neurol. 442:266–276, 2002.

Reducing the Uncertainty: Gating of Peripheral Inputs by Zona Incerta

Sensory inputs are relayed to the neocortex by “first-order” thalamic nuclei, the responses of which are determined by ascending inputs from peripheral receptors. In contrast, “higher-order” thalamic nuclei respond poorly to peripheral inputs, and their responses are thought to be determined by descending cortical inputs. We tested this hypothesis by recording from neurons in the higher-order somatosensory posterior medial (POm) nucleus of narcotized rats. As reported previously, POm neurons responded to whisker stimuli with long-latency (median, 27 msec) and low-magnitude responses, consistent with cortically driven responses. However, when we suppressed inhibitory inputs from the subthalamic nucleus zona incerta (ZI), POm responses were of significantly higher magnitude and shorter latency, with many POm neurons responding at latencies consistent with ascending driving inputs from trigeminal nuclei. Our data suggest that POm comprises two neuronal populations: one population is driven by both peripheral and cortical inputs, and the second population responds only to cortical inputs. These findings demonstrate that ZI gates peripheral inputs to POm, enabling it to function both as a first-order and higher-order nucleus. Because ZI innervates all higher-order nuclei, this gating mechanism may exert similar regulation of thalamic processing in other sensory systems.

Membrane Bistability in Olfactory Bulb Mitral Cells

Whole-cell patch-clamp recordings were used to investigate the electrophysiological properties of mitral cells in rat main olfactory bulb brain slice preparations. The majority of mitral cells are bistable. These cells spontaneously alternate between two membrane potentials, separated by ∼10 mV: a relatively depolarized potential (upstate), which is perithreshold for spike generation, and a relatively hyperpolarized potential (downstate), in which spikes do not occur. Bistability occurs spontaneously in the absence of ionotropic excitatory or inhibitory synaptic inputs. Bistability is voltage dependent; transition from the downstate to the upstate is a regenerative event activated by brief depolarization. A brief hyperpolarization can switch the membrane potential from the upstate to the downstate. In response to olfactory nerve (ON) stimulation, mitral cells in the upstate are more likely to fire an action potential than are those in the downstate. ON stimulation can switch the membrane potential from the downstate to the upstate, producing a prolonged and amplified depolarization in response to a brief synaptic input. We conclude that bistability is an intrinsic property of mitral cells that is a major determinant of their responses to ON input.

Neuronal mechanisms of motor learning in mammals.

Neural mechanisms subserving the acquisition of new motor skills are discussed in this article. Motor learning is defined, in this context, as the acquisition of novel motor skills. It is proposed that complex motor skills are acquired through a process of segmental motor learning, in which movement segments are formed, and retrieved for the execution of the learned skill. Individual movement segments are created by modulating neural activity in loop circuits that link the motor cortex and the periphery. This neural modulation occurs through synaptic plasticity in the motor cortex. Increase of synaptic efficacy in existing neural circuits, in the form of long-term potentiation (LTP), is proposed to be involved in earlier stages of motor learning. It is suggested that the retention of motor skills involves formation of new synapses.

Neonatal whisker clipping alters intracortical, but not thalamocortical projections, in rat barrel cortex.

Retrograde axonal transport of cholera toxin B subunit (CTB) was used to compare the development of intracortical and thalamocortical connections in normal rats with those in rats in which all of the whiskers were trimmed continuously from birth. In normal animals, injections of CTB into a single barrel column resulted in an asymmetrical labeling of cells that were distributed preferentially within columns related to the same row in which the injection was placed. This anisotropy in the patterns of intracortical connections was not observed in whisker‐clipped animals. In these animals, there was a significant reduction in the mean number of labeled cells in the infragranular layers, and labeled cells were distributed symmetrically around the injection site. The same injections of CTB also labeled thalamocortical neurons in the ventrobasal thalamus. Analysis of the distribution of these cells revealed that, in both control and experimental animals, the vast majority of labeled cells were restricted to a homologous (i.e., corresponding to the injected cortical barrel) thalamic barreloid. These findings indicate that manipulations of sensory experience alter patterns of intracortical, but not thalamocortical, connections. J. Comp. Neurol. 412:83–94, 1999.

Whisker motor cortex ablation and whisker movement patterns

Previous studies, based on qualitative observations, reported that lesions of the whisker motor cortex produce no deficits in whisking behavior. We used high-resolution optoelectronic recording methods to compare the temporal organization and kinematics of whisker movements before and after unilateral lesions of whisker motor cortex in rats. We now report that while the lesion did not abolish whisking, it significantly disrupted whisking kinematics, coordination, and temporal organization. Lesioned animals showed significant increases in the velocity and amplitude of whisker protractions contralateral to the lesions, as well as a reduction in the synchrony of whisker movements on the two sides of the face. There was a marked shift in the distribution of whisking frequencies, with reduction of activity in the 5–7 Hz bandwidth and increased activity at < 2 Hz. Disruptions of the normal whisking pattern were evident on both sides of the face, and the magnitude of these effects was proportional to the extent of the cortical ablation. We suggest that the observed deficits reflect an imbalance in cortical inputs to a brainstem central pattern generator.

Intrinsic connections between representation zones in the cat motor cortex

The functional organization of intrinsic connections in the cat motor cortex was examined by combining intracortical microstimulation with neuroanatomical tracers. After single injections of a dye into a cortical site from which wrist flexion was evoked, clusters of retrogradely labeled somata and of anterogradely labeled axon terminals were found throughout the forelimb representation zones. These intrinsic connections rarely involved representation zones of the hindlimb or the face musculature. These data indicate that extensive intracortical connections mediate reciprocal synaptic interactions among groups of cells involved in the execution of different movement segments. These clustered, horizontal connections may be used for coordinating the activity of different cortical representations for the execution of complex movements, and may also be involved in the pliability of motor representation maps.

The Role of Thalamic Inputs in Surround Receptive Fields of Barrel Neurons

Controversy exists regarding the relative roles of thalamic versus intracortical inputs in shaping the response properties of cortical neurons. In the whisker-barrel system, this controversy centers on the mechanisms determining the receptive fields of layer IV (barrel) neurons. Whereas principal whisker-evoked responses are determined by thalamic inputs, the mechanisms responsible for adjacent whisker (AW) responses are in dispute. Here, we took advantage of the fact that lesions of the spinal trigeminal nucleus interpolaris (SpVi) significantly reduce the receptive field size of neurons in the ventroposterior thalamus. We reasoned that if AW responses are established by these thalamic inputs, brainstem lesions would significantly reduce the receptive field sizes of barrel neurons. We obtained extracellular single unit recordings from barrel neurons in response to whisker deflections from control rats and from rats that sustained SpVi lesions. After SpVi lesions, the receptive field of both excitatory and inhibitory barrel neurons decreased significantly in size, whereas offset/onset response ratios increased. Response magnitude decreased only for inhibitory neurons. All of these findings are consistent with the hypothesis that AW responses are determined primarily by direct thalamic inputs and not by intracortical interactions.

Superior Colliculus Control of Vibrissa Movements

This study tested the role of the superior colliculus in generating movements of the mystacial vibrissae--whisking. First, we compared the kinematics of whisking generated by the superior colliculus with those generated by the motor cortex. We found that in anesthetized rats, microstimulation of the colliculus evoked a sustained vibrissa protraction, whereas stimulation of motor cortex produced rhythmic protractions. Movements generated by the superior colliculus are independent of motor cortex and can be evoked at lower thresholds and shorter latencies than those generated by the motor cortex. Next we tested the hypothesis that the colliculus is acting as a simple reflex loop with the neurons that drive vibrissa movement receiving sensory input evoked by vibrissa contacts. We found that most tecto-facial neurons do not receive sensory input. Not only did these neurons not spike in response to sensory stimulation, but field potential analysis revealed that subthreshold sensory inputs do not overlap spatially with tecto-facial neurons. Together these findings suggest that the superior colliculus plays a pivotal role in vibrissa movement--regulating vibrissa set point and whisk amplitude--but does not function as a simple reflex loop. With the motor cortex controlling the whisking frequency, the superior colliculus control of set point and amplitude would account for the main parameters of voluntary whisking.

Superior sensation: superior colliculus participation in rat vibrissa system.

BackgroundThe superior colliculus, usually considered a visuomotor structure, is anatomically positioned to perform sensorimotor transformations in other modalities. While there is evidence for its potential participation in sensorimotor loops of the rodent vibrissa system, little is known about its functional role in vibrissa sensation or movement. In anesthetized rats, we characterized extracellularly recorded responses of collicular neurons to different types of vibrissa stimuli.ResultsCollicular neurons had large receptive fields (median = 14.5 vibrissae). Single units displayed responses with short latencies (5.6 ± 0.2 msec, median = 5.5) and relatively large magnitudes (1.2 ± 0.1 spikes/stimulus, median = 1.2). Individual neurons could entrain to repetitive vibrissa stimuli delivered at ≤ 20 Hz, with little reduction in phase locking, even when response magnitude was decreased. Neurons responded preferentially to vibrissa deflections at particular angles, with 43% of the cells having high (≥ 5) angular selectivity indices.ConclusionResults are consistent with a proposed role of the colliculus in somatosensory-mediated orienting. These properties, together with the connections of the superior colliculus in sensorimotor loops, are consistent with its involvement in orienting, alerting and attentive functions related to the vibrissa system.