Processing of information from the parafascicular nucleus of the thalamus through the basal ganglia.

Accumulating evidence implicates the parafascicular nucleus of the thalamus (Pf) in basal ganglia (BG)-related functions and pathologies. Despite Pf connectivity with all BG components, most attention is focused on the thalamostriatal system and an integrated view of thalamic information processing in this network is still lacking. Here, we addressed this question by recording the responses elicited by Pf activation in single neurons of the substantia nigra pars reticulata (SNr), the main BG output structure in rodents, in anesthetized mice. We performed optogenetic activation of Pf neurons innervating the striatum, the subthalamic nucleus (STN), or the SNr using virally mediated transcellular delivery of Cre from injection in either target in Rosa26-LoxP-stop-ChR2-EYFP mice to drive channelrhodopsin expression. Photoactivation of Pf neurons connecting the striatum evoked an inhibition often followed by an excitation, likely resulting from the activation of the trans-striatal direct and indirect pathways, respectively. Photoactivation of Pf neurons connecting the SNr or the STN triggered one or two early excitations, suggesting partial functional overlap of trans-subthalamic and direct thalamonigral projections. Excitations were followed in about half of the cases by an inhibition that might reflect recruitment of intranigral inhibitory loops. Finally, global Pf stimulation, electrical or optogenetic, elicited similar complex responses comprising up to four components: one or two short-latency excitations, an inhibition, and a late excitation. These data provide evidence for functional connections between the Pf and different BG components and for convergence of the information processed through these pathways in single SNr neurons, stressing their importance in regulating BG outflow.

Distinct Cortical-Thalamic-Striatal Circuits through the Parafascicular Nucleus.

The thalamic parafascicular nucleus (PF), an excitatory input to the basal ganglia, is targeted with deep-brain stimulation to alleviate a range of neuropsychiatric symptoms. Furthermore, PF lesions disrupt the execution of correct motor actions in uncertain environments. Nevertheless, the circuitry of the PF and its contribution to action selection are poorly understood. We find that, in mice, PF has the highest density of striatum-projecting neurons among all sub-cortical structures. This projection arises from transcriptionally and physiologically distinct classes of PF neurons that are also reciprocally connected with functionally distinct cortical regions, differentially innervate striatal neurons, and are not synaptically connected in PF. Thus, mouse PF contains heterogeneous neurons that are organized into parallel and independent associative, limbic, and somatosensory circuits. Furthermore, these subcircuits share motifs of cortical-PF-cortical and cortical-PF-striatum organization that allow each PF subregion, via its precise connectivity with cortex, to coordinate diverse inputs to striatum.

Robust interactions between the effects of auditory and cutaneous electrical stimulations on cell activities in the thalamic reticular nucleus.

The thalamic reticular nucleus (TRN), a cluster of GABAergic cells, is thought to regulate bottom-up and top-down streams of sensory processing in the loop circuitry between the thalamus and cortex. Provided that sensory inputs of different modalities interact in the TRN, the TRN could contribute to fast and flexible cross-modal modulation of attention and perception that incessantly takes place in our everyday life. Indeed, diverse subthreshold interactions of auditory and visual inputs have been revealed in TRN cells (Kimura, 2014). To determine whether such sensory interaction could extend across modalities as a universal neural mechanism, the present study examined TRN cell activities elicited by auditory and cutaneous electrical stimulations in anesthetized rats. Juxta-cellular recording and labeling techniques were used. Recordings were obtained from 129 cells. Auditory or somatosensory responses were modulated by subthreshold electrical stimulation or sound (noise burst) in the majority of recordings (77 of 85 auditory and 13 of 15 somatosensory cells). Additionally, 22 bimodal cells and seven cells that responded only to combined stimulation were recognized. Suppression was predominant in modulation that was observed in both early and repeatedly evoked late responses. Combined stimulation also induced de novo cell activities. Further, response latency and burst spiking were modulated. Axonal projections of cells showing modulation terminated in first- or higher-order thalamic nuclei. Nine auditory cells projected to somatosensory thalamic nuclei. These results suggest that the TRN could regulate sensory processing in the loop circuitry between the thalamus and cortex through the sensory interaction pervasive across modalities.

Dynamics of coupled thalamocortical modules.

We develop a model of thalamocortical dynamics using a shared population of thalamic neurons to couple distant cortical regions. Behavior of the model is determined as a function of the connection strengths with shared and unshared populations in the thalamus, either within a relay nucleus or the reticular nucleus. When the coupling is via the reticular nucleus, we locate solutions of the model where distant cortical regions maintain the same activity level, and regions where one region maintains an elevated activity level, suppressing activity in the other. We locate and investigate a region where both types of solutions exist and are stable, yielding a mechanism for spontaneous changes in global activity patterns. Power spectra and coherence are computed, and marked differences in the coherence are found between the two kinds of modes. When, on the other hand, the coupling is via a shared relay nuclei, the features seen with the reticular coupling are absent. These considerations suggest a role for the reticular nucleus in modulating long distance cortical communication.

Acoustic stress activates tuberoinfundibular peptide of 39 residues neurons in the rat brain.

Strong acoustic stimulation (105 dB SPL white noise) elicited c-fos expression in neurons in several acoustic system nuclei and in stress-sensitive hypothalamic nuclei and limbic areas in rats. In the present study, using this type of loud noise for 30 min, Fos-like immunoreactivity (Fos-ir) was investigated in neurons that synthesize tuberoinfundibular peptide of 39 residues (TIP39) in the rat brain: in the subparafascicular area of the thalamus, the posterior intralaminar complex of the thalamus and the medial paralemniscal nucleus in the lateral part of the pons. By double labeling, Fos-ir was shown in nearly 80% of TIP39-positive cells in the medial paralemniscal nucleus, 43% in the posterior intralaminar complex and 18.5% in the subparafascicular area 30 min after the end of a 30-min loud noise period. In control rats, only few neurons, including 0-4% of TIP39-positive neurons showed Fos-ir. While the majority of the Fos-ir neurons were TIP39-positive in the subparafascicular area and medial paralemniscal nucleus, a fairly high number of TIP39-immunonegative, chemically uncharacterized neurons expressed c-fos in the subparafascicular area and the posterior intralaminar complex of the thalamus. These observations clearly show that some TIP39 neurons in the so-called "acoustic thalamus" and the majority of TIP39 neurons in the medial paralemniscal nucleus are sensitive to loud noise and they may participate in the central organization of responses to acoustic stress. Furthermore, the present data suggest that non-TIP39-expressing neurons may play a prevalent role in the activity of the "acoustic thalamus".

A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures.

Neural inhibition within the thalamus is integral in shaping thalamocortical oscillatory activity. Fast, synaptic inhibition is primarily mediated by activation of heteropentameric GABA(A) receptor complexes. Here, we examined the synaptic physiology and network properties of mice lacking GABA(A) receptor alpha3, a subunit that in thalamus is uniquely expressed by inhibitory neurons of the reticular nucleus (nRT). Deletion of this subunit produced a powerful compensatory gain in inhibitory postsynaptic response in nRT neurons. Although, other forms of inhibitory and excitatory synaptic transmission in the circuit were unchanged, evoked thalamic oscillations were strongly dampened in alpha3 knockout mice. Furthermore, pharmacologically induced thalamocortical absence seizures displayed a reduction in length and power in alpha3 knockout mice. These studies highlight the role of GABAergic inhibitory strength within nRT in the maintenance of thalamic oscillations, and demonstrate that inhibitory intra-nRT synapses are a critical control point for regulating higher order thalamocortical network activity.

Cholinergic innervation and thalamic input in rat nucleus accumbens.

Cholinergic interneurons are the only known source of acetylcholine in the rat nucleus accumbens (nAcb); yet there is little anatomical data about their mode of innervation and the origin of their excitatory drive. We characterized the cholinergic and thalamic innervations of nAcb with choline acetyltransferase (ChAT) immunocytochemistry and anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L) from the midline/intralaminar/paraventricular thalamic nuclei. The use of a monoclonal ChAT antiserum against whole rat ChAT protein allowed for an optimal visualization of the small dendritic branches and fine varicose axons of cholinergic interneurons. PHA-L-labeled thalamic afferents were heterogeneously distributed throughout the core and shell regions of nAcb, overlapping regionally with cholinergic somata and dendrites. At the ultrastructural level, several hundred single-section profiles of PHA-L and ChAT-labeled axon terminals were analyzed for morphology, synaptic frequency, and the nature of their synaptic targets. The cholinergic profiles were small and apposed to various neuronal elements, but rarely exhibited a synaptic membrane specialization (5% in single ultrathin sections). Stereological extrapolation indicated that less than 15% of these cholinergic varicosities were synaptic. The PHA-L-labeled profiles were comparatively large and often synaptic (37% in single ultrathin sections), making asymmetrical contacts primarily with dendritic spines (>90%). Stereological extrapolation indicated that all PHA-L-labeled terminals were synaptic. In double-labeled material, some PHA-L-labeled terminals were directly apposed to ChAT-labeled somata or dendrites, but synapses were never seen between the two types of elements. These observations demonstrate that the cholinergic innervation of rat nAcb is largely asynaptic. They confirm that the afferents from midline/intralaminar/paraventricular thalamic nuclei to rat nAcb synapse mostly on dendritic spines, presumably of medium spiny neurons, and suggest that the excitatory drive of nAcb cholinergic interneurons from thalamus is indirect, either via substance P release from recurrent collaterals of medium spiny neurons and/or by extrasynaptic diffusion of glutamate.

Roles of the thalamic CM-PF complex-Basal ganglia circuit in externally driven rebias of action.

The centromedian (CM)-parafascicular (PF) nuclear complex in the primate thalamus has reciprocal and specific connections with the basal ganglia. It has been argued that the thalamic CM-PF complex has a role in pain processing and attention. However, the functional relationship of this complex with the basal ganglia, which is considered to have a role in goal-directed movement, has not been well characterized. Here we present a hypothetical view that the thalamic CM-PF complex-basal ganglia circuit plays complementary roles in response bias. The basal ganglia are involved in creating 'reward-based pre-action bias', which facilitates the selection and execution of an action associated with a higher value. In contrast, when an action with a lower value is unexpectedly requested, the CM-PF induces an 'externally driven rebiasing' process in the striatum that aborts the pre-action bias and assists selecting and executing actions appropriate for unexpected situations. This model provides a framework for how the thalamic CM-PF complex and the basal ganglia function together in general for unexpected situations.

The primate centromedian-parafascicular complex: anatomical organization with a note on neuromodulation.

In addition to the cerebral cortex, the striatum receives excitatory input from the thalamus. The centromedian (centre median, CM) and parafascicular (Pf) nuclei are an important source of thalamostriatal projections. Anterograde tract-tracing indicates the CM-Pf complex provides dense afferents to the matrix compartment of the striatum. Whereas CM projects to the entire sensorimotor territory of the striatum, the Pf provides complementary input to the entire associative sector. The Pf also provides lighter input to the nucleus accumbens. Both CM and Pf provide light to moderately dense inputs to other components of the basal ganglia in a largely complementary manner, covering motor or associative-limbic territories of the subthalamic nucleus, globus pallidus and ventral midbrain. In turn, the CM and Pf receive mainly segregated input from parallel motor and associative-limbic circuits of the basal ganglia. The CM and Pf may therefore be considered important participants in parallel processing of motor and associative-limbic information in the basal ganglia. Connections of the CM and Pf with other thalamic nuclei suggest they also participate in integrative functions within the thalamus. In addition, inputs from the brainstem reticular core, reciprocal connections with the cerebral cortex and reticular thalamic nucleus suggest a role in state-dependant information processing. Consideration of the differential connections of the CM and Pf, and better understanding of their role in pathophysiology, may eventually lead to development of an important new target for relief of a variety of neurological and psychiatric disorders.

Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with Lennox-Gastaut syndrome.

PURPOSE: Our aim was to evaluate the efficacy of ESCM (electrical stimulation of the centromedian thalamic nucleus) in treatment of generalized seizures of the Lennox-Gastaut syndrome (LGS) and improvement of patient disability. METHODS: Thirteen patients with LGS were studied. They had severe generalized tonic-clonic seizures (GTC) and atypical absences (AA). All patients had at least a 6-month baseline before bilateral electrode implantation to the centromedian (CM) nuclei of the thalamus to undergo therapeutic ESCM. Once implanted, electrodes were temporally externalized through a retromastoid point for electrophysiologic confirmation of their placement. After target confirmation, stimulation parameters were set. Patients came for follow-up assessment of seizures and neurophysiologic tests every 3 months during an 18-month period of time; AED therapy was not modified. RESULTS: The surgical procedure as well as electrical stimulation was well tolerated by all patients. No side effects occurred with the therapeutic stimulation parameters used, and patients were not aware of device activation. Two patients were explanted because of repeated and multiple skin erosions that could not be controlled by plastic surgery procedures. Overall seizure reduction was 80%. The three patients with poorest outcomes for seizure control did not improve their ability scale score. In contrast, the two patients rendered seizure free are living a normal life at present. The remaining eight patients experienced progressive improvement, from being totally disabled to becoming independent in five cases and partially dependent in two. Patients with adequate electrode placement had a seizure reduction >87%. To consider that an electrode is correctly placed, both stereotactic placement and neurophysiologic responses are taken into account. CONCLUSIONS: ESCM provides a nonlesional, neuromodulatory method with improvement in seizure outcome and in the abilities of patients with severe LGS.

A computational model of how an interaction between the thalamocortical and thalamic reticular neurons transforms the low-frequency oscillations of the globus pallidus.

In Parkinson's disease, neurons of the internal segment of the globus pallidus (GPi) display the low-frequency tremor-related oscillations. These oscillatory activities are transmitted to the thalamic relay nuclei. Computer models of the interacting thalamocortical (TC) and thalamic reticular (RE) neurons were used to explore how the TC-RE network processes the low-frequency oscillations of the GPi neurons. The simulation results show that, by an interaction between the TC and RE neurons, the TC-RE network transforms a low-frequency oscillatory activity of the GPi neurons to a higher frequency of oscillatory activity of the TC neurons (the superharmonic frequency transformation). In addition to the interaction between the TC and RE neurons, the low-threshold calcium current in the RE and TC neurons and the hyperpolarization-activated cation current (I (h)) in the TC neurons have significant roles in the superharmonic frequency transformation property of the TC-RE network. The external globus pallidus (GPe) oscillatory activity, which is directly transmitted to the RE nucleus also displays a significant modulatory effect on the superharmonic frequency transformation property of the TC-RE network.

Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder.

OBJECTIVE: Our aim was to study electrocortical and behavioral responses elicited by 6, 60 and 3/s stimulation of the inferior thalamic peduncle (ITP) and nucleus reticularis thalami (Re) in a patient with of major depression disorder resistant to psychotherapy, pharmacotherapy and electroconvulsive therapy and candidate to be treated by electrical stimulation of the ITP. METHODS: In this patient, two multicontact electrodes were implanted bilaterally through frontal coronal parasagittal burr-holes with oblique trajectories aiming ITP and Re. Stimulation was performed through externalized systems. Referential scalp electroencephalographic (EEG) recordings were performed and subjective sensations and clinical symptoms reported by patient and changes in responsiveness in single response tasks during stimulation trials were systematically recorded. RESULTS: Unilateral, low (6/s) and high (60/s) frequency stimulation of either ITP or Re produced identical recruiting-like responses or desynchronization-DC shift changes predominant at frontopolar region, bilaterally. Billateral, high intensity 3/s stimulation or either ITP or Re produced electrocortical responses that consisted in generalized 3/s spike-wave complexes predominant at frontopolar, frontocentral and frontotemporal regions. However, while ITP responses were accompanied by all symptoms described for a spontaneous absence attack, Re responses were behaviorly accompanied only by delayed reaction time. CONCLUSION: These data suggests that in humans as in cats, ITP and Re are both part of a non-specific thalamo-orbitofrontal system normally engaged in cortical synchronization, selective attention and sleep. SIGNIFICANCE: Under abnormal conditions, ITP and RE may play a role in the physiopathology of typical absence attacks and depression disorders.

The role of temporal parameters in a thalamocortical model of analogy.

How multiple specialized cortical areas in the brain interact with each other to give rise to an integrated behavior is a largely unanswered question. This paper proposes that such an integration can be understood under the framework of analogy and that part of the thalamus and the thalamic reticular nucleus (TRN) may be playing a key role in this respect. The proposed thalamocortical model of analogy heavily depends on a diverse set of temporal parameters including axonal delay and membrane time constant, each of which is critical for the proper functioning of the model. The model requires a specific set of conditions derived from the need of the model to process analogies. Computational results with a network of integrate and fire (IF) neurons suggest that these conditions are indeed necessary, and furthermore, data found in the experimental literature also support these conditions. The model suggests that there is a very good reason for each temporal parameter in the thalamocortical network having a particular value, and that to understand the integrated behavior of the brain, we need to study these parameters simultaneously, not separately.

Center median-parafascicular complex and pain control. Review from a neurosurgical perspective.

The center median-parafascicular (CM-Pf) complex, which constitutes the major portion of the intralaminar thalamus in man, has long been known to be involved in the processing of pain under normal and pathological conditions. Yet, these 'forgotten' nuclei with their rich connectivity to other thalamic nuclei, the basal ganglia and cortical areas have received only relatively little attention over the past two decades. With regard to the recent reinterest in functional stereotactic neurosurgery as a treatment option for chronic refractory pain, the CM-Pf complex has been reconsidered as a target. This review provides a systematic overview on the current knowledge about the anatomy and connectivity of the CM-Pf complex, neurophysiological studies, and on concepts of its role in pain processing under various conditions. We also review the previous experience with ablative surgery and deep brain stimulation of the CM-Pf complex. Studies in men and experimental animals indicate that the CM-Pf complex is part of a medial pain system, which appears to be involved primarily in affective and motivational dimensions of pain. Single-unit recordings from the CM-Pf complex have shown that the activity of CM-Pf cells is modified by painful stimuli. Under pathological conditions, bursting firing patterns and altered discharge rates were found. Thalamotomies targeting at the CM-Pf complex yielded beneficial results for chronic pain, but interpretation of the results is limited. With bifocal deep brain stimulation, short-term effects of CM-Pf stimulation were superior to those of somatosensory thalamic stimulation in neuropathic pain. There is evidence, that the CM-Pf complex might also be involved in the mediation of the beneficial effects of somatosensory thalamic stimulation and periventricular grey stimulation.

Suppression of limbic motor seizures by electrical stimulation in thalamic reticular nucleus.

Kindling is a model of temporal lobe epilepsy in which repeated electrical stimulations in limbic areas lead to progressive increase of seizure susceptibility, culminating in generalized convulsions and the establishment of a permanent epileptic syndrome. We studied here the effect of stimulations in the thalamic reticular nucleus (TRN) on the development of seizures and hippocampal hyperexcitability in kindling elicited from the ventral hippocampus in rats. Animals given 12 kindling stimulations per day with 30-min intervals for 4 consecutive days developed generalized convulsions on day 4. Stimulations in TRN delivered simultaneously with those in the hippocampus induced marked suppression of seizure generalization. Similarly, the number of generalized seizures and the duration of behavioral convulsions were reduced when rats subjected to 40 kindling stimulations with 5-min intervals during about 3 h were costimulated in the TRN. The anticonvulsant effect of TRN costimulation was detected also when rats were test-stimulated in the hippocampus at 24 h and 2 and 4 weeks after the initial 40 hippocampal stimulations. Our data provide the first evidence that TRN stimulations can act to suppress limbic motor seizures in hippocampal kindling and suggest a new approach for seizure control in temporal lobe epilepsy.

Thalamocortical and intracortical connections of monkey cingulate motor areas.

Although there has been an increasing interest in motor functions of the cingulate motor areas, data concerning their input organization are still limited. To address this issue, the patterns of thalamic and cortical inputs to the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas were investigated in the macaque monkey. Tracer injections were made into identified forelimb representations of these areas, and the distributions of retrogradely labeled neurons were analyzed in the thalamus and the frontal cortex. The cells of origin of thalamocortical projections to the CMAr were located mainly in the parvicellular division of the ventroanterior nucleus and the oral division of the ventrolateral nucleus (VLo). On the other hand, the thalamocortical neurons to the CMAd/CMAv were distributed predominantly in the VLo and the oral division of the ventroposterolateral nucleus-the caudal division of the ventrolateral nucleus. Additionally, many neurons in the intralaminar nuclear group were seen to project to the cingulate motor areas. Except for their well-developed interconnections, the corticocortical projections to the CMAr and CMAd/CMAv were also distinctively preferential. Major inputs to the CMAr arose from the presupplementary motor area and the dorsal premotor cortex, whereas inputs to the CMAd/CMAv originated not only from these areas but also from the supplementary motor area and the primary motor cortex. The present results indicate that the CMAr and the caudal cingulate motor area (involving both the CMAd and the CMAv) are characterized by distinct patterns of thalamocortical and intracortical connections, reflecting their functional differences.

Reticular thalamic responses to nociceptive inputs in anesthetized rats.

The present study compares nociceptive responses of neurons in the reticular thalamic nucleus (RT) to those of the ventroposterior lateral nucleus (VPL). Extracellular single-unit activities of cells in the RT and VPL were recorded in anesthetized rats. Only units with identified tactile receptive fields in the forepaw or hindpaw were studied. In the first series of experiments, RT and VPL responses to pinching with a small artery clamp were tested with the rats under pentobarbital, urethane, ketamine, or halothane anesthesia. Under all types of anesthesia, many RT units were inhibited. Second, the specificity of the nociceptive response was tested by pinching and noxious heating of the unit's tactile receptive field. Of the 39 VPL units tested, 20 were excited by both types of noxious stimuli. In sharp contrast, of the 30 RT units tested, none were excited and 17 were inhibited. In a third series of experiments, low-intensity and beam-diffused CO(2) laser irradiation was used to activate peripheral nociceptive afferents. Wide-dynamic-range VPL units responded with short- and long-latency excitations. In contrast, RT units had short-latency excitation followed by long-latency inhibition. Nociceptive input inhibited RT units in less than 500 ms. We conclude that a significant portion of RT neurons were polysynaptically inhibited by nociceptive inputs. Since all the cells tested were excited by light tactile inputs, the somatosensory RT may serve in the role of a modality gate, which modifies (i.e. inhibits) tactile inputs while letting noxious inputs pass.

Auditory sensory gating in hippocampus and reticular thalamic neurons in anesthetized rats.

BACKGROUND: Auditory gating is thought to reflect sensory information processing and is absent or diminished in schizophrenic patients. Although abnormal thalamic sensory processing has been proposed in schizophrenia, sensory gating of thalamic neurons has not been demonstrated experimentally. The aim of the present study was to establish whether auditory gating is present in the rat thalamus using a well-characterized animal model of auditory gating and schizophrenia. METHODS: Hippocampal electroencephalogram and single-unit activity in the thalamic reticular nucleus (nRT) were recorded in anaesthetized rats. Evoked potentials in the hippocampus and neuronal activity in the nRT were monitored in response to bilateral auditory stimuli. The effects of the psychostimulant D-amphetamine and the antipsychotic haloperidol on auditory gating were evaluated. RESULTS: Thalamic reticular nucleus neurons showed gated responses to paired-tone auditory stimuli, resembling hippocampal auditory gating. D-amphetamine disrupted auditory gating of nRT neurons and abolished their burst activity. D-amphetamine also disrupted hippocampal auditory gating and induced hippocampal theta activity. The amphetamine-induced gating deficit was reversed by haloperidol in both regions. CONCLUSIONS: Our findings provide the first experimental evidence for auditory gating of nRT neurons. We demonstrated that amphetamine disrupts sensory processing of nRT neurons, indicating similarities between hippocampal and thalamic sensory gating. These findings support the presumed connection between dopamine hyperfunction and abnormal thalamic filtering in schizophrenia.

The thalamic reticular nucleus: more than a sensory nucleus?

Sensory information is routed to the cortex via the thalamus, but despite this sensory bombardment, animals must attend selectively to stimuli that signal danger or opportunity. Sensory input must be filtered, allowing only behaviorally relevant information to capture limited attentional resources. Located between the thalamus and cortex is a thin lamina of neurons called the thalamic reticular nucleus (Rt). The thalamic reticular nucleus projects exclusively to thalamus, thus forming an essential component of the circuitry mediating sensory transmission. This article presents evidence supporting a role for Rt beyond the mere relay of sensory information. Rather than operating as a component of the sensory relay, the authors suggest that Rt represents an inhibitory interface or "attentional gate," which regulates the flow of information between the thalamus and cortex. Recent findings have also implicated Rt in higher cognitive functions, including learning, memory, and spatial cognition. Drawing from recent insights into the dynamic nature of the thalamic relay in awake, behaving animals, the authors present a speculative account of how Rt might regulate thalamocortical transmission and ultimately the contents of consciousness.