Ventral Posterior Medial Neurons Research Articles

Brain-State-Dependent Modulation of Neuronal Firing and Membrane Potential Dynamics in the Somatosensory Thalamus during Natural Sleep

The thalamus plays a central role in sleep rhythms in the mammalian brain and, yet, surprisingly little is known about its function and interaction with local cortical oscillations during NREM sleep (NREM). We investigated the neuronal correlates of cortical barrel activity in the two corresponding thalamic nuclei, the ventral posterior medial (VPM), and the posterior medial (Pom) nuclei during natural NREM in mice. Our data reveal (1) distinct modulations of VPM and Pom activity throughout NREM episodes, (2) a thalamic nucleus-specific phase-locking to cortical slow and spindle waves, (3) cell-specific subthreshold spindle oscillations in VPM neurons that only partially overlap with cortical spindles, and (4) that spindle features evolve throughout NREM episodes and vary according to the post-NREM state. Taken together, our results suggest that, during natural sleep, the barrel cortex exerts a leading role in the generation and transfer of slow rhythms to the somatosensory thalamus and reciprocally for spindle oscillations.

Whisking in air: Encoding of kinematics by VPM neurons in awake rats

Rodent whisking behavior generates two types of neural signals: one produced by whisker contact with objects; the other by movements in air. While kinematic signals generated by contact reliably activate neurons at all levels of the trigeminal neuraxis, the extent to which the kinematics of whisking in air are reliably encoded at each level remains unclear. Previously, we showed that the responses of trigeminal ganglion (TG) neurons in awake, head-fixed rats are correlated with whisking kinematic parameters, but that individual neurons may differ substantially in the reliability of their kinematic encoding. Here, we extend that analysis to neurons in the ventral posterior medial (VPM) nucleus. Three possible coding strategies were examined: (1) firing rate across an entire movement; (2) the probability of individual spikes as a function of the instantaneous movement trajectory; and (3) the coherence between spikes and whisking. While VPM neurons were clearly responsive to variations in whisker kinematics during whisking in air, the encoding of whisker kinematics by VPM neurons was less consistent than that of TG neurons. Furthermore, we found that, in VPM as in TG, movement direction is an important determinant of unit responsiveness during whisking in air.

Cortical modulation of spatial and angular tuning maps in the rat thalamus.

The massive feedback projections from cortex to the thalamus modulate sensory information transmission in many ways. We investigated the role of corticothalamic feedback projections on the directional selectivity (angular tuning) of neurons in the rat ventral posterior medial (VPM) nucleus to stimulation of their principal whisker. The angular tuning properties of single VPM neurons were compared before and after epochs of electrical stimulation of layer VI feedback neurons in the ipsilateral cortex under urethane anesthesia. Microstimulation of layer VI in "matched" (homologous) barrel columns sharpens the angular tuning curves of single VPM neurons that are tuned to the same direction as the stimulation site in the cortex. Further, microstimulation rotates the angular preference of VPM neurons initially tuned to a different direction toward the direction that cortical neurons prefer. Stimulation in "mismatched" (nonhomologous) barrel columns suppresses responses without consistent effects on angular tuning. We conclude that the primary sensory cortex exerts a significant influence on both spatial and angular tuning maps in the relay nuclei that project to it. The results suggest that the tuning properties of VPM cells in the behaving animal are continually modified to optimize perception of the most salient incoming messages.

Balancing bilateral sensory activity: callosal processing modulates sensory transmission through the contralateral thalamus by altering the response threshold

Rats tactually explore a nearly spherical space field around their heads with their whiskers. The information sampled by the two sets of whiskers is integrated bilaterally at the cortical level in an activity dependent manner via the corpus callosum. We have recently shown that sensory activity in one barrel field cortex (BFC) modulates the processing of incoming sensory information to the other BFC. Whether interhemispheric integration is dynamically linked with corticothalamic modulation of incoming sensory activity is an important hypothesis to test, since subcortical relay neurons are directly modulated by cortical neurons through top-down processes. In the present study, we compared the direct sensory responses of single thalamic relay neurons under urethane anesthesia before and after inactivating the BFC contralateral to a thalamic neuron. The data show that silencing one BFC reduces response magnitude in contralateral thalamic relay neurons, significantly and reversibly, in response to test stimuli applied to the principal whisker at two times response threshold (2T) intensity for each unit. Neurons in the ventral posterior medial (VPM) nucleus and the medial division of the posterior nucleus (POm) react in a similar manner, although POm neurons are more profoundly depressed by inactivation of the contralateral BFC than VPM neurons. The results support the novel idea that the subcortical relay of sensory information to one hemisphere is strongly modulated by activity levels in the contralateral as well as in the ipsilateral SI cortex. The mechanism of the modulation appears to be based on shifting the stimulus-response curves of thalamic neurons, thereby rendering them more or less sensitive to sensory stimuli. We conclude that global sensory processing is created by combining activity in each cerebral hemisphere and continually balancing the flow of information to cortex by adjusting the responsiveness of ascending sensory pathways.

The contribution of the principal and spinal trigeminal nuclei to the receptive field properties of thalamic VPM neurons in the rat.

Primary sensory information from neurons innervating whisker follicles on one side of a rat's face is relayed primarily through two subnuclei of the brainstem trigeminal complex to the contralateral thalamus. The present experiments were undertaken to separate the contribution of the principal trigeminal nucleus (PrV) from that of the spinal trigeminal nucleus (SpV) to whisker evoked responses in the ventral posterior medial (VPM) nucleus in the adult rat thalamus. Extracellular single-unit responses of VPM neurons to controlled stimulation of the contralateral whiskers under urethane anesthesia were quantified in terms of receptive field size, modal latency, response probability and response magnitude. The SpV contribution to VPM cell responses was isolated by making kainic acid lesions of the PrV. The PrV contribution was ascertained by cutting the trigeminothalamic axons arising from SpV just before they cross the midline. After destruction of the PrV, the SpV pathway alone produced large receptive fields (mean: 9.04 whiskers) and long latency (mean: 11.07 ms) responses from VPM neurons. In contrast, PrV input alone (SpV disconnected) generated small receptive fields (mean: 1.06 whiskers) and shorter latency (mean: 6.74 ms) responses. With both pathways intact the average receptive field size was 2.4 whiskers and peak (modal) response latency was 7.33 ms. The responses with both pathways intact were significantly different from either pathway operating in isolation. Response probability and magnitude followed the same trend. We conclude that normal responses of individual VPM neurons represent the integration of input activity transmitted through both PrV and SpV pathways.

Thalamocortical [correction of Thalamcortical] optimization of tactile processing according to behavioral state.

We propose a conceptual model that describes the operation of the main thalamocortical loop of the rat somatosensory system. According to this model, the asynchronous convergence of ascending and descending projections dynamically alters the physiological properties of thalamic neurons in the ventral posterior medial (VPM) nucleus as rats shift between three behavioral states. Two of these states are characterized by distinct modes of rhythmic whisker movements. We posit that these simultaneous shifts in exploratory behavioral strategy and in the physiological properties of VPM neurons allow rats to either (i) optimize the detection of stimuli that are novel or difficult to sense or (ii) process complex patterns of multi-whisker stimulation.

Role of cortical feedback in the receptive field structure and nonlinear response properties of somatosensory thalamic neurons.

Previous studies have suggested that the descending pathway from the primary somatosensory (SI) cortex to the ventral posterior nucleus of the thalamus has only a mild facilitative influence over thalamic neurons. Given the large numbers of corticothalamic terminations within the rat somatosensory thalamus and their complex topography, we sought to examine the role of corticothalamic feedback in the genesis of spatiotemporal receptive fields and the integration of complex tactile stimuli in the thalamus. By combining focal cortical inactivation (produced by microinjection of the GABA(A) agonist muscimol), with chronic multielectrode recordings, we observed that feedback from the rat SI cortex has multiple influences on its primary thalamic relay, the ventral posterior medial (VPM) nucleus. Our data demonstrate that, when single-whisker stimuli were used, the elimination of cortical feedback caused significant changes in the spatiotemporal structure of the receptive fields of VPM neurons. Cortical feedback also accounted for the nonlinear summation of VPM neural responses to simultaneously stimulated whiskers, in effect "linearizing" the responses. These results argue that the integration and transmission of tactile information through VPM are strongly influenced by the state of SI cortex.

Modulation of receptive field properties of thalamic somatosensory neurons by the depth of anesthesia.

Modulation of receptive field properties of thalamic somatosensory neurons by the depth of anesthesia. The dominant frequency of electrocorticographic (ECoG) recordings was used to determine the depth of halothane or urethan anesthesia while recording extracellular single-unit responses from thalamic ventral posterior medial (VPM) neurons. A piezoelectric stimulator was used to deflect individual whiskers to assess the peak onset latency, magnitude, probability of response, and receptive field (RF) size. There was a predictable increase in the dominant ECoG frequency from deep stage IV to light stage III-1 anesthetic levels. There was no detectable frequency at stage IV, a 1- to 2-Hz dominant frequency at stage III-4, 3-4 Hz at stage III-3, 5-7 Hz at stage III-2, and a dual 6- and 10- to 13-Hz pattern at stage III-1. Reflexes and other physical signs showed a correlation with depth of anesthesia but exhibited too much overlap between stages to be used as a criterion for any single stage. RF size and peak onset latency of VPM neurons to whisker stimulations increased between stage III-4 and III-1. A dramatic increase in RF size and response latency occurred at the transition from stage III-3 (RF size approximately 2 whiskers, latency approximately 7 ms) to stage III-2 (RF size approximately 6 whiskers, latency approximately 11 ms). Response probability and magnitude decreased from stage III-4 to stage III-3 and III-2. No responses were ever evoked in VPM cells by vibrissa movement at stage IV. These changes in VPM responses as a function of anesthetic depth were seen only when the nucleus principalis (PrV) and nucleus interpolaris (SpVi) trigeminothalamic pathways were both intact. Eliminating SpVi inputs to VPM, either by cutting the primary trigeminal afferent fibers to SpVi or cutting axons projecting from SpVi to VPM, immediately reduced the RF size to fewer than three whiskers. In addition, the predictable changes in VPM response probability, response magnitude, and peak onset latency at different anesthetic depths were all absent after SpVi pathway interruption. We conclude that 1) the PrV input mediates the near "one-to-one" correspondence between a neuronal response in VPM and a single mystacial whisker, 2) in contrast, the SpVi input to VPM is primarily responsible for the RF properties of VPM neurons at light levels of anesthesia and presumably in the awake animal, and 3) alterations in VPM responses produced by changing the depth of anesthesia are due to its selective influence on the properties mediated by SpVi inputs at the level of the thalamus.

Spatiotemporal structure of somatosensory responses of many-neuron ensembles in the rat ventral posterior medial nucleus of the thalamus

Classically, the rat ventral posterior medial (VPM) nucleus of the thalamus has been considered as a simple passive relay for single-whisker information to the primary somatosensory cortex (SI). However, recent reports have suggested that the VPM could contain a much more coarsely coded and spatiotemporally complex representation of the rat whisker pad. To address this possibility properly, we have carried out chronic simultaneous recordings of large numbers (up to 23) of single neurons, distributed across the entire VPM, in both awake and lightly anesthetized adult rats. Quantitative, computer-based reconstruction of receptive fields (RFs) revealed that single VPM neurons exhibit significant responses to discrete stimulation of as many as 20 single whiskers (mean +/- SD RF size, 13.7 +/- 4.8 whiskers). By defining multiple response magnitude (RM) thresholds it was possible to subdivide these large VPM RFs quantitatively into a prominent center (mean +/- SD, 1.41 +/- 0.70 whiskers, RM > 95%) and an excitatory surround (up to 18 whiskers, RM < 95%). VPM neurons exhibited both short-latency responses (SLRs, from 4 to 10 msec poststimulus) and/or long-latency responses (LLRs, 15-25 msec), each followed by inhibitory responses. Though LLRs were weaker (mean +/- SD, 47.19 +/- 33.34 Hz) than SLRs (119.63 +/- 50.12 Hz), they often defined RFs that differed considerably from those defined by the SLRs of the same cell. In particular, VPM cells with short-latency RFs centered in caudal whiskers (e.g., C1, D1, E1) showed a poststimulus time-dependent shift of these RF centers toward the rostral whiskers (e.g., C4, D4, E4). These caudal-to-rostral (C-->RF shifts occurred in neurons with the largest RFs of our sample (17.2 +/- 2.4 whiskers). On the other hand, VPM cells with short-latency RFs centered in rostral whiskers had the smallest RFs (13.1 +/- 4.1 whiskers) and usually did not exhibit time-dependent RF center shifts. Multivariate analysis revealed that these two groups of VPM neurons, C-->R shifting and rostral position (RP) cells, could be statistically distinguished according to a combination of three RF attributes (short-latency RF center location, RF size, and magnitude of RF center shift). Quantitative, computer-based reconstruction of "population response maps" demonstrated that the "place" coding for each single whisker in the VPM involved a distinct weighted contribution from a large proportion of the simultaneously recorded neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons.

1. Changes in the response properties of 106 ventral posterior medial (VPM) units were assessed after iontophoretic blockade of gamma-aminobutyric acid-A or -B (GABAA or GABAB) receptor-mediated inhibition using bicuculline methiodide (BIC) or 2-hydroxy-saclofen (2-OH-S), respectively. 2. The iontophoretic administration of either BIC or 2-OH-S did not alter significantly the average spontaneous firing rate of VPM neurons for current intensities between 40 and 80 nA. The presence of 10 mM 2-OH-S (60 nA) was effective in completely reversing the depressant effects of the selective GABAB receptor agonist, baclofen, on the spontaneous activity of VPM neurons. 3. The effect of BIC on whisker-evoked responses was a preferential enhancement in the responses elicited by the whisker giving rise to the highest probability response (center receptive field whisker or CRF). The effect of 2-OH-S (40-80 nA iontophoretic currents) was to increase the responsiveness of VPM neurons to the stimulation of whiskers in all parts of the receptive field (RF), although its influence was much more pronounced in the peripheral areas of the RF (surround receptive field whisker or SRF). This preferential enhancement of SRF-whisker responses after the blockade of GABAB receptor-mediated inhibition resulted in a 2.3-fold increase in the average RF size of VPM neurons; no statistically significant increases in the size of the RF were seen in the presence of BIC. 4. The primary influence of BIC and, to a lesser degree, 2-OH-S was to prolong the response duration of VPM neurons to CRF whisker stimulation. Under our recording conditions, approximately 25% of VPM neurons in normal animals responded with sustained discharges. In the presence of BIC and 2-OH-S, the percent of VPM units that could be classified as tonically responding increased to 82% and 67%, respectively. 5. The proportion of VPM neurons that was selective to the deflection of whiskers in a particular direction (87%) was not altered in the presence of BIC or 2-OH-S. 6. BIC was effective in antagonizing GABA-mediated inhibition within the first 40 ms of a stimulus; BIC was completely ineffective in reversing a late suppression seen between 80 and 140 ms. In contrast, no statistically significant changes in the initial GABA-mediated inhibition were seen in the presence of 2-OH-S, but 2-OH-S was partially effective in antagonizing the late suppression of responses in VPM neurons.(ABSTRACT TRUNCATED AT 400 WORDS)