Cortex dynamically modulates responses of thalamic relay neurons through prolonged circuit-level disinhibition in rat thalamus in vivo

Cortex actively modulates the responses of thalamic relay neurons through corticothalamic (CT) projections. Here we investigated the temporal precision of CT modulation on sensory responses of relay neurons in rat ventral posterior medial thalamus (VPM) to direction-specific whisker stimuli. CT feedback levels were either augmented by cortical electrical microstimulation or depressed by cortical application of muscimol, a potent agonist of γ-aminobutyric acid A-type (GABAA) receptors. To evaluate the temporal specificity of CT influence, we compared the early (3–10 ms after stimulus onset) and late (10–100 ms) response components of VPM single units to whisker deflections in preferred or nonpreferred directions before and after altering CT feedback levels under urethane anesthesia. The data showed that cortical feedback most strongly affected the late responses of single VPM units to whisker stimulation. That is, cortical stimulation consistently increased the late responses of VPM units in the corresponding (homologous) barreloids to the stimulus direction preferred by neurons in the cortical locus stimulated. However, cortical stimulation could either increase or decrease the early response, depending on whether or not cortical and thalamic loci were tuned to the same direction. Such bidirectional regulation of the early and late VPM responses is consistent with a mechanism of circuit-level disinhibition in vivo. The results support the theory that CT feedback on thalamic sensory responses is mediated by a time-dependent shift of the excitation-inhibition balance in the thalamo-cortico-thalamic loop, such as would occur during sensory feature integration, plasticity, and learning in the awake state.

Substantia Nigra Output to Prefrontal Cortex Via Thalamus in Monkeys. II. Activity of Thalamic Relay Neurons in Delayed Conditional Go/No-Go Discrimination Task

The present report investigated the involvement of primate nigro-thalamo-cortical projections in discrimination of visual signals with behavioral meaning. We tested the extracellular unit activity of mediodorsal (MD) and ventral anterior (VA) thalamic neurons monosynaptically receiving inhibitory input from the substantia nigra pars reticulata (SNr) and projecting to the frontal cortex in Japanese monkeys performing a delayed conditional go/no-go discrimination task. In the task two colored stimuli (S1, S2) intervened by delay period required the monkeys lifting a lever (go) or not (no-go); the same and different colored pairs of S1 and S2 meant go and no-go signals, respectively. Prominent task-relevant responses were sustained activity with color preference to S1 during delay period and S2-related activity with different firing rates between go and no-go trials. In particular, a high proportion of such go/no-go differential S2-related activity was found in thalamic relay neurons, receiving input from the caudolateral SNr and projecting to the prefrontal area (PSv) ventral to the principal sulcus, in the rostrolateral MD. The findings suggest that the caudolateral SNr–rostrolateral MD–PSv pathways may be possible conduits of signals coding the behavioral meaning of the visual stimuli and thus may be responsible for generating similar neuronal activity in the PSv.

Substantia Nigra Output to Prefrontal Cortex Via Thalamus in Monkeys. I. Electrophysiological Identification of Thalamic Relay Neurons

A few studies have been performed in primate basal ganglia–thalamo–prefrontal pathways. Nevertheless, their electrophysiological properties and anatomical arrangements remain obscure. This study examined them in nigro-thalamo-cortical pathways from the substantia nigra pars reticulata (SNr) to the frontal cortex (FRC) via the mediodorsal (MD) and ventral anterior (VA) thalamus in monkeys. First, single thalamocortical neurons with SNr input were identified by antidromic responses to FRC stimulation and by inhibitory orthodromic responses with short latencies (<5 ms) to SNr stimulation. Second, single nigrothalamic neurons were found by antidromic responses to stimulation of the portions of the MD and VA where the thalamocortical neurons were recorded. The inhibitory orthodromic responses in the thalamocortical neurons were considered to be monosynaptically induced by nigral stimulation because the latency distribution of the orthodromic responses in the thalamocortical neurons was similar to that of the antidromic responses in the nigrothalamic neurons. Almost all relay neurons in the rostrolateral MD received inhibitory afferents from the caudolateral SNr and projected to the prefrontal area ventral to the principal sulcus, which constituted the densest nigro-thalamo-cortical projections. Meanwhile, neurons in the VA received inhibitory signals from the whole rostrocaudal extent of the SNr and projected to wide regions of the FRC; neurons in its pars magnocellularis mostly projected to different prefrontal areas, while those in its pars parvocellularis projected to motor areas. This report substantiated the topography of thalamocortical neurons monosynaptically receiving inhibitory SNr input and projecting to the FRC in the primate MD and VA at the single-neuron level.

Deregulation of the balance between data and conceptually driven processing: A shift toward the conceptual

Behrendt & Young (B&Y) propose that a dysfunction in the reticular thalamic nucleus contributes to disinhibition of specific thalamic nuclei, allowing cortical attention mechanisms to engage thalamic relay neurons, causing underconstrained activation of the cortex and hallucinations. The following hypothesis challenges the notion of impaired sensory gating by providing the alternative view that hypofrontality reduces the power of incoming stimuli, causing internal drives to override consciousness, resulting in hallucinations.