Responses of neurons in the primary somatosensory cortex to itch- and pain-producing stimuli in rats.

Understanding of cortical encoding of itch is limited. Injection of pruritogens and algogens into the skin of the cheek produces distinct behaviors, making the rodent cheek a useful model for understanding mechanisms of itch and pain. We examined responses of neurons in the primary somatosensory cortex by application of mechanical stimuli (brush, pressure, and pinch) and stimulations with intradermal injections of pruritic and algesic chemical of receptive fields located on the skin of the cheek in urethane-anesthetized rats. Stimuli included chloroquine, serotonin, ß-alanine, histamine, capsaicin, and mustard oil. All 33 neurons studied were excited by noxious mechanical stimuli applied to the cheek. Based on mechanical stimulation most neurons were functionally classified as high threshold. Of 31 neurons tested for response to chemical stimuli, 84% were activated by one or more pruritogens/partial pruritogens. No cells were activated by all five substances. Histamine activated the greatest percentage of neurons and evoked the greatest mean discharge. Importantly, no cells were excited exclusively by pruritogens or partial pruritogens. The recording sites of all neurons that responded to chemical stimuli applied to the cheek were located in the dysgranular zone (DZ) and in deep laminae of the medial border of the vibrissal barrel fields (VBF). Therefore, neurons in the DZ/VBF of rats encode mechanical and chemical pruritogens and algogens. This cortical region appears to contain primarily nociceptive neurons as defined by responses to noxious pinching of the skin. Its role in encoding itch and pain from the cheek of the face needs further study.NEW & NOTEWORTHY Processing of information related to itch sensation at the level of cerebral cortex is not well understood. In this first single-unit electrophysiological study of pruriceptive cortical neurons, we show that neurons responsive to noxious and pruritic stimulation of the cheek of the face are concentrated in a small area of the dysgranular cortex, indicating that these neurons encode information related to itch and pain.

The Zona Incerta Regulates Communication between the Superior Colliculus and the Posteromedial Thalamus: Implications for Thalamic Interactions with the Dorsolateral Striatum.

There is uncertainty concerning the circuit connections by which the superior colliculus interacts with the basal ganglia. To address this issue, anterograde and retrograde tracers were placed, respectively, into the superior colliculus and globus pallidus of Sprague-Dawley rats. In this two-tracer experiment, the projections from the superior colliculus terminated densely in the ventral zona incerta (ZIv), but did not overlap the labeled neurons observed in the subthalamic nucleus. In cases in which anterograde and retrograde tracers were placed, respectively, in sensory-responsive sites in the superior colliculus and posteromedial (POm) thalamus, the labeled projections from superior colliculus innervated the ZIv regions that contained the labeled neurons that project to POm. We also confirmed this colliculo-incertal-POm pathway by depositing a mixture of retrograde and anterograde tracers at focal sites in ZIv to reveal retrogradely labeled neurons in superior colliculus and anterogradely labeled terminals in POm. When combined with retrograde tracer injections in POm, immunohistochemical processing proved that most ZIv projections to POm are GABAergic. Consistent with these findings, direct stimulation of superior colliculus evoked neuronal excitation in ZIv and caused inhibition of spontaneous activity in POm. Collectively, these results indicate that superior colliculus can activate the inhibitory projections from ZIv to the POm. This is significant because it suggests that the superior colliculus could suppress the interactions between POm and the dorsolateral striatum, presumably to halt ongoing behaviors so that more adaptive motor actions are selected in response to unexpected sensory events. SIGNIFICANCE STATEMENT: By demonstrating that the zona incerta regulates communication between the superior colliculus and the posteromedial thalamus, we have uncovered a circuit that partly explains the behavioral changes that occur in response to unexpected sensory stimuli. Furthermore, this circuit could explain why deep brain stimulation of the zona incerta is beneficial to patients who suffer from Parkinson's disease.

Mapping the functional network of medial prefrontal cortex by combining optogenetics and fMRI in awake rats.

The medial prefrontal cortex (mPFC) plays a critical role in multiple cognitive and limbic functions. Given its vital importance, investigating the function of individual mPFC circuits in animal models has provided critical insight into the neural basis underlying different behaviors and psychiatric conditions. However, our knowledge regarding the mPFC whole-brain network stays largely at the anatomical level, while the functional network of mPFC, which can be dynamic in different conditions or following manipulations, remains elusive especially in awake rodents. Here we combined optogenetic stimulation and functional magnetic resonance imaging (opto-fMRI) to reveal the network of brain regions functionally activated by mPFC outputs in awake rodents. Our data showed significant increases in blood-oxygenation-level dependent (BOLD) signals in prefrontal, striatal and limbic regions when mPFC was optically stimulated. This activation pattern was robust, reproducible, and did not depend on the stimulation period in awake rats. BOLD signals, however, were substantially reduced when animals were anesthetized. In addition, regional brain activation showing increased BOLD signals during mPFC stimulation was corroborated by electrophysiological recordings. These results expand the applicability of the opto-fMRI approach from sensorimotor processing to cognition-related networks in awake rodents. Importantly, it may help elucidate the circuit mechanisms underlying numerous mPFC-related functions and behaviors that need to be assessed in the awake state.

Thalamostriatal projections from the medial posterior and parafascicular nuclei have distinct topographic and physiologic properties.

The dorsolateral striatum (DLS) is critical for executing sensorimotor behaviors that depend on stimulus-response (S-R) associations. In rats, the DLS receives it densest inputs from primary somatosensory (SI) cortex, but it also receives substantial input from the thalamus. Much of rat DLS is devoted to processing whisker-related information, and thalamic projections to these whisker-responsive DLS regions originate from the parafascicular (Pf) and medial posterior (POm) nuclei. To determine which thalamic nucleus is better suited for mediating S-R associations in the DLS, we compared their input-output connections and neuronal responses to repetitive whisker stimulation. Tracing experiments demonstrate that POm projects specifically to the DLS, but the Pf innervates both dorsolateral and dorsomedial parts of the striatum. The Pf nucleus is innervated by whisker-sensitive sites in the superior colliculus, and these sites also send dense projections to the zona incerta, a thalamic region that sends inhibitory projections to the POm. These data suggest that projections from POm to the DLS are suppressed by incertal inputs when the superior colliculus is activated by unexpected sensory stimuli. Simultaneous recordings with two electrodes indicate that POm neurons are more responsive and habituate significantly less than Pf neurons during repetitive whisker stimulation. Response latencies are also shorter in POm than in Pf, which is consistent with the fact that Pf receives its whisker information via synaptic relays in the superior colliculus. These findings indicate that, compared with the Pf nucleus, POm transmits somatosensory information to the DLS with a higher degree of sensory fidelity.

Functional architecture of the forebrain cholinergic system in rodents.

The basal forebrain cholinergic system (BFCS) participates in functions that are global across the brain, such as sleep-wake cycles, but also participates in capacities that are more behaviorally and anatomically specific, including sensory perception. To better understand the underlying organization principles of the BFCS, more and higher quality anatomical data and analysis is needed. Here, we created a "virtual Basal Forebrain", combining data from numerous rats with cortical retrograde tracer injections into a common 3D reference coordinate space and developed a "spatial density correlation" methodology to analyze patterns in BFCS cortical projection targets, revealing that the BFCS is organized into three principal networks: somatosensory-motor, auditory, and visual. Within each network, clusters of cholinergic cells with increasing complexity innervate cortical targets. These networks represent hierarchically organized building blocks that may enable the BFCS to coordinate spatially selective signaling, including parallel modulation of multiple functionally interconnected yet diverse groups of cortical areas.

Rat claustrum coordinates but does not integrate somatosensory and motor cortical information.

The function of the claustrum is a fundamental issue in neuroscience. Anatomical data indicate that the rat claustrum is part of an interhemispheric circuit that could be involved in the bilateral coordination of whisker movements. Given that whisking is a somesthetic-guided motor behavior, the goal of the current study was to elucidate the connections of the claustrum with respect to the whisker representations in the primary somatosensory (wSI) and motor (wMI) cortical areas. Anterograde tracer injections showed that wMI projects most densely to the claustrum in the contralateral hemisphere, whereas wSI does not project to the claustrum in either hemisphere. Injections of different retrograde tracers into wMI and wSI of the same animal revealed intermingled populations of labeled neurons in the claustrum, as well as many double-labeled neurons. This indicates that the same part of the claustrum projects to the whisker representations in both SI and MI. Finally, injections of different anterograde tracers in the wMI regions of both hemispheres were combined with a retrograde tracer injection in wSI, and this produced dense terminal labeling around retrogradely labeled neurons in the claustrum of both hemispheres. Although the rodent claustrum is probably involved in the interhemispheric coordination of the MI and SI whisker representations, it does not receive inputs from both of these cortical regions. Hence, the claustrum should not be universally regarded as an integrator of somesthetic and motor information.

Thalamic POm projections to the dorsolateral striatum of rats: potential pathway for mediating stimulus-response associations for sensorimotor habits.

The dorsolateral part of the striatum (DLS) represents the initial stage for processing sensorimotor information in the basal ganglia. Although the DLS receives much of its input from the primary somatosensory (SI) cortex, peripheral somesthetic stimulation activates the DLS at latencies that are shorter than the response latencies recorded in the SI cortex. To identify the subcortical regions that transmit somesthetic information directly to the DLS, we deposited small quantities of retrograde tracers at DLS sites that displayed consistent time-locked responses to controlled whisker stimulation. The neurons that were retrogradely labeled by these injections were located mainly in the sensorimotor cortex and, to a lesser degree, in the amygdala and thalamus. Quantitative analysis of neuronal labeling in the thalamus indicated that the strongest thalamic input to the whisker-sensitive part of the DLS originates from the medial posterior nucleus (POm), a somesthetic-related region that receives inputs from the spinal trigeminal nucleus. Anterograde tracer injections in POm confirmed that this thalamic region projects to the DLS neuropil. In subsequent experiments, simultaneous recordings from POm and the DLS during whisker stimulation showed that POm consistently responds before the DLS. These results suggest that POm could transmit somesthetic information to the DLS, and this modality-specific thalamostriatal pathway may cooperate with the thalamostriatal projections that originate from the intralaminar nuclei.

Convergence of forepaw somatosensory and motor cortical projections in the striatum, claustrum, thalamus, and pontine nuclei of cats.

The basal ganglia and pontocerebellar systems regulate somesthetic-guided motor behaviors and receive prominent inputs from sensorimotor cortex. In addition, the claustrum and thalamus are forebrain subcortical structures that have connections with somatosensory and motor cortices. Our previous studies in rats have shown that primary and secondary somatosensory cortex (S1 and S2) send overlapping projections to the neostriatum and pontine nuclei, whereas, overlap of primary motor cortex (M1) and S1 was much weaker. In addition, we have shown that M1, but not S1, projects to the claustrum in rats. The goal of the current study was to compare these rodent projection patterns with connections in cats, a mammalian species that evolved in a separate phylogenetic superorder. Three different anterograde tracers were injected into the physiologically identified forepaw representations of M1, S1, and S2 in cats. Labeled fibers terminated throughout the ipsilateral striatum (caudate and putamen), claustrum, thalamus, and pontine nuclei. Digital reconstructions of tracer labeling allowed us to quantify both the normalized distribution of labeling in each subcortical area from each tracer injection, as well as the amount of tracer overlap. Surprisingly, in contrast to our previous findings in rodents, we observed M1 and S1 projections converging prominently in striatum and pons, whereas, S1 and S2 overlap was much weaker. Furthermore, whereas, rat S1 does not project to claustrum, we confirmed dense claustral inputs from S1 in cats. These findings suggest that the basal ganglia, claustrum, and pontocerebellar systems in rat and cat have evolved distinct patterns of sensorimotor cortical convergence.

Functional specificity of claustrum connections in the rat: interhemispheric communication between specific parts of motor cortex.

Recent evidence indicates that the rat claustrum interconnects the motor cortical areas in both hemispheres. To elucidate the functional specificity of the interhemispheric connections between the claustrum and primary motor (MI) cortex, anterograde tracer injections in specific parts of MI were paired with retrograde tracer injections in homotopic sites of the opposite hemisphere. In addition to injecting the MI forepaw (Fp) region in both hemispheres, we injected the region associated with whisker retractions (Re) and the more caudal rhythmic whisking (RW) region. While the MI-Fp region has few connections with the claustrum of either hemisphere, both whisker regions project to the contralateral claustrum, with those from the MI-RW region being denser and more extensive than those originating from the MI-Re region. Retrograde tracer injections in the MI-RW region produced more labeled neurons in the ipsilateral claustrum than retrograde tracer injections in the MI-Re. Consistent with these patterns, the overlap of labeled terminals and soma in the claustrum was greatest when both tracers were injected into the MI-RW region. When retrograde tracers were injected into the claustrum, the highest density of labeled neurons in MI appeared in the contralateral RW region. Tracer injections in the claustrum also revealed hundreds of labeled neurons throughout its rostrocaudal extent, thereby establishing the presence of long-range intraclaustral connections. These results indicate that the intrinsic and extrinsic connections of the rat claustrum are structured for rapid, interhemispheric transmission of information needed for bilateral coordination of the MI regions that regulate whisker movements.

Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits.

The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neurons in the DLS responded to both directions of movement. The latency and magnitude of these neuronal responses displayed very little variation with changes in the rate (2, 5, or 8 Hz) of whisker stimulation. Simultaneous recordings in SI barrel cortex and the DLS revealed important distinctions in the neuronal responses of these serially connected brain regions. In contrast to DLS neurons, SI neurons were activated by the initial deflection of the whiskers but did not respond when the whiskers moved back to their original position. As the rate of whisker stimulation increased, SI responsiveness declined, and the latencies of the responses increased. In fact, when whiskers were deflected at 5 or 8 Hz, many neurons in the DLS responded before the SI neurons. These results and earlier anatomic findings suggest that a component of the sensory-induced response in the DLS is mediated by inputs from the thalamus. Furthermore, the lack of sensory adaptation in the DLS may represent a critical part of the neural mechanism by which the DLS encodes stimulus-response associations that trigger motor habits and other stimulus-evoked behaviors that are not contingent on rewarded outcomes.

Information processing streams in rodent barrel cortex: the differential functions of barrel and septal circuits.

Rodent somatosensory cortex contains an isomorphic map of the mystacial whiskers in which each whisker is represented by neuronal populations, or barrels, that are separated from each other by intervening septa. Separate afferent pathways convey somatosensory information to the barrels and septa that represent the input stages for 2 partially segregated circuits that extend throughout the other layers of barrel cortex. Whereas the barrel-related circuits process spatiotemporal information generated by whisker contact with external objects, the septa-related circuits encode the frequency and other kinetic features of active whisker movements. The projection patterns from barrel cortex indicate that information processed by the septa-related circuits is used both separately and in combination with information from the barrel-related circuits to mediate specific functions. According to this theory, outputs from the septal processing stream modulate the brain regions that regulate whisking behavior, whereas both processing streams cooperate with each other to identify external stimuli encountered by passive or active whisker movements. This theoretical view prompts several testable hypotheses about the coordination of neuronal activity during whisking behavior. Foremost among these, motor brain regions that control whisker movements are more strongly coordinated with the septa-related circuits than with the barrel-related circuits.

A Role for the Claustrum in Salience Processing?

The claustrum (CLA) is a subcortical structure, present only in mammals, whose function remains uncertain. Previously, using resting-state functional magnetic resonance imaging (rs-fMRI) in awake head-fixed rats, we found evidence that the CLA is part of the rodent homolog of the default mode network (DMN; Smith et al., 2017). This network emerged as strong functional connections between the medial prefrontal cortex (mPFC), mediodorsal (MD) thalamus, and CLA in the awake state, which was not present following administration of isoflurane anesthesia. In the present report, we review evidence indicating that the rodent CLA also has connections with structures identified in the rodent homolog of the salience network (SN), a circuit that directs attention towards the most relevant stimuli among a multitude of sensory inputs (Seeley et al., 2007; Menon and Uddin, 2010). In humans, this circuit consists of functional connections between the anterior cingulate cortex (ACC) and a region that encompasses both the CLA and insular cortex. We further go on to review the similarities and differences between the functional and anatomical connections of the CLA and insula in rodents using both rs-fMRI and neuroanatomical tracing, respectively. We analyze in detail the connectivity of the CLA with the cingulate cortex, which is a major node in the SN and has been shown to modulate attention. When considered with other recent behavior and physiology studies, the data reveal a role for the CLA in salience-guided orienting. More specifically, we hypothesize that limbic information from mPFC, MD thalamus, and the basolateral amygdala (BLA) are integrated by the CLA to guide modality-related regions of motor and sensory cortex in directing attention towards relevant (i.e., salient) sensory events.

The relationship between the claustrum and endopiriform nucleus: A perspective towards consensus on cross-species homology.

With the emergence of interest in studying the claustrum, a recent special issue of the Journal of Comparative Neurology dedicated to the claustrum (Volume 525, Issue 6, pp. 1313-1513) brought to light questions concerning the relationship between the claustrum (CLA) and a region immediately ventral known as the endopiriform nucleus (En). These structures have been identified as separate entities in rodents but appear as a single continuous structure in primates. During the recent Society for Claustrum Research meeting, a panel of experts presented data pertaining to the relationship of these regions and held a discussion on whether the CLA and En should be considered (a) separate unrelated structures, (b) separate nuclei within the same formation, or (c) subregions of a continuous structure. This review article summarizes that discussion, presenting comparisons of the cytoarchitecture, neurochemical profiles, genetic markers, and anatomical connectivity of the CLA and En across several mammalian species. In rodents, we conclude that the CLA and the dorsal endopiriform nucleus (DEn) are subregions of a larger complex, which likely performs analogous computations and exert similar effects on their respective cortical targets (e.g., sensorimotor versus limbic). Moving forward, we recommend that the field retain the nomenclature currently employed for this region but should continue to examine the delineation of these structures across different species. Using thorough descriptions of a variety of anatomical features, this review offers a clear definition of the CLA and En in rodents, which provides a framework for identifying homologous structures in primates.

Opposing collicular influences on the parafascicular (Pf) and posteromedial (POm) thalamic nuclei: relationship to POm-induced inhibition in the substantia nigra pars reticulata (SNR).

The superior colliculus activates the zona incerta (ZI), which sends GABAergic projections to the posteromedial (POm) thalamic nucleus. Consistent with this circuit, we previously showed that stimulation of the superior colliculus activates ZI and causes inhibition of neuronal activity in POm (Watson et al., J Neurosci 35:9463-9476, 2015). Other studies, however, have shown that collicular stimulation activates the intralaminar nuclei of the thalamus. The present study extends these reports by showing that unilateral collicular stimulation causes bilateral activation of Pf that is concomitant with bilateral inhibition of POm. The opposing influences of the superior colliculus on Pf and POm are significant, because both these thalamic nuclei innervate the striatum, which is involved in behavioral selection. In view of data indicating that thalamostriatal projections from Pf and other intralaminar nuclei increase the sensitivity of the indirect pathway to corticostriatal inputs (Ding et al., Neuron 67:294-307, 2010), we tested whether POm stimulation might exert an opposing influence on the basal ganglia circuitry. Consistent with POm projections to the dorsolateral striatum (DLS), which is necessary for the expression of sensorimotor habits, we found that POm stimulation activates DLS and causes inhibition of neuronal activity in the lateral part of the substantia nigra pars reticulata, which is a major target of DLS and the direct pathway. These findings are discussed with respect to clinical reports indicating that deep brain stimulation in ZI is effective in reducing the symptoms of Parkinson's disease.

The systemDrive: a Multisite, Multiregion Microdrive with Independent Drive Axis Angling for Chronic Multimodal Systems Neuroscience Recordings in Freely Behaving Animals.

A multielectrode system that can address widely separated targets at multiple sites across multiple brain regions with independent implant angling is needed to investigate neural function and signaling in systems and circuits of small animals. Here, we present the systemDrive, a novel multisite, multiregion microdrive that is capable of moving microwire electrode bundles into targets along independent and nonparallel drive trajectories. Our design decouples the stereotaxic surgical placement of individual guide cannulas for each trajectory from the placement of a flexible drive structure. This separation enables placement of many microwire multitrodes along widely spaced and independent drive axes with user-set electrode trajectories and depths from a single microdrive body, and achieves stereotaxic precision with each. The system leverages tight tube-cannula tolerances and geometric constraints on flexible drive axes to ensure concentric alignment of electrode bundles within guide cannulas. Additionally, the headmount and microdrive both have an open-center design to allow for the placement of additional sensing modalities. This design is the first, in the context of small rodent chronic research, to provide the capability to finely position microwires through multiple widely distributed cell groups, each with stereotaxic precision, along arbitrary and nonparallel trajectories that are not restricted to emanate from a single source. We demonstrate the use of the systemDrive in male Long-Evans rats to observe simultaneous single-unit and multiunit activity from multiple widely separated sleep-wake regulatory brainstem cell groups, along with cortical and hippocampal activity, during free behavior over multiple many-day continuous recording periods.

The premammillary nucleus of the hypothalamus is not necessary for photoperiodic timekeeping in female turkeys (Meleagris gallopavo).

In birds, seasonal reproduction is regulated by day length, with long days in the spring activating the hypothalamic-pituitary-gonadal axis and reproductive behaviors. The photoreceptors mediating this process remain unknown, but recently, the premammillary nucleus (PMM) of the hypothalamus has been implicated as the site of photoperiodic signaling in turkeys. We performed electrolytic lesions of the PMM to elucidate its role in the photoactivation and maintenance of egg production in female turkeys. Our results show that ablation of the PMM does not alter the normal lay cycle. No differences were found between lesioned birds and sham controls in the latency to lay following photostimulation, nor in subsequent egg production over a period of 29 weeks. No differences in the incidence of gonadal regression were found, indicating that the PMM is not essential for the termination of breeding. We conclude that any role of the PMM in photoperiodic regulation, if it exists, is redundant with other components of the system.

Interhemispheric connections between the infralimbic and entorhinal cortices: The endopiriform nucleus has limbic connections that parallel the sensory and motor connections of the claustrum.

We have previously shown that the claustrum is part of an interhemispheric circuit that interconnects somesthetic-motor and visual-motor cortical regions. The role of the claustrum in processing limbic information, however, is poorly understood. Some evidence suggests that the dorsal endopiriform nucleus (DEn), which lies immediately ventral to the claustrum, has connections with limbic cortical areas and should be considered part of a claustrum-DEn complex. To determine whether DEn has similar patterns of cortical connections as the claustrum, we used anterograde and retrograde tracing techniques to elucidate the connectivity of DEn. Following injections of retrograde tracers into DEn, labeled neurons appeared bilaterally in the infralimbic (IL) cortex and ipsilaterally in the entorhinal and piriform cortices. Anterograde tracer injections in DEn revealed labeled terminals in the same cortical regions, but only in the ipsilateral hemisphere. These tracer injections also revealed extensive longitudinal projections throughout the rostrocaudal extent of the nucleus. Dual retrograde tracer injections into IL and lateral entorhinal cortex (LEnt) revealed intermingling of labeled neurons in ipsilateral DEn, including many double-labeled neurons. In other experiments, anterograde and retrograde tracers were separately injected into IL of each hemisphere of the same animal. This revealed an interhemispheric circuit in which IL projects bilaterally to DEn, with the densest terminal labeling appearing in the contralateral hemisphere around retrogradely labeled neurons that project to IL in that hemisphere. By showing that DEn and claustrum have parallel sets of connections, these results suggest that DEn and claustrum perform similar functions in processing limbic and sensorimotor information, respectively. J. Comp. Neurol. 525:1363-1380, 2017. © 2016 Wiley Periodicals, Inc.

Interhemispheric resting-state functional connectivity of the claustrum in the awake and anesthetized states.

The claustrum is a brain region whose function remains unknown, though many investigators suggest it plays a role in conscious attention. Resting-state functional magnetic resonance imaging (RS-fMRI) has revealed how anesthesia alters many functional connections in the brain, but the functional role of the claustrum with respect to the awake versus anesthetized states remains unknown. Therefore, we employed a combination of seed-based RS-fMRI and neuroanatomical tracing to reveal how the anatomical connections of the claustrum are related to its functional connectivity during quiet wakefulness and the isoflurane-induced anesthetic state. In awake rats, RS-fMRI indicates that the claustrum has interhemispheric functional connections with the mediodorsal thalamus (MD) and medial prefrontal cortex (mPFC), as well as other known connections with cortical areas that correspond to the connections revealed by neuroanatomical tracing. During deep isoflurane anesthesia, the functional connections of the claustrum with mPFC and MD were significantly attenuated, while those with the rest of cortex were not significantly altered. These changes in claustral functional connectivity were also observed when seeds were placed in mPFC or MD during RS-fMRI comparisons of the awake and deeply anesthetized states. Collectively, these data indicate that the claustrum has functional connections with mPFC and MD-thalamus that are significantly lessened by anesthesia.

Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways.

The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson's disease (PD) and related neurological disorders.

Differential origin of projections from SI barrel cortex to the whisker representations in SII and MI.

We have previously shown that projections from SI barrel cortex to the MI whisker representation originate primarily from columns of neurons that are aligned with the layer IV septa. SI barrel cortex also projects to SII cortex, but the origin of these projections has not been characterized with respect to the barrel and septal compartments. To address this issue, we injected retrograde tracers into the SII whisker representation and then reconstructed the location of the labeled neurons in SI with respect to the layer IV barrels. In some animals, two different tracers were injected into the whisker representations of SII and MI to detect double-labeled neurons that would indicate that some SI neurons project to both of these cortical areas. We found that the projections to SII cortex originate from sites that are uniformly distributed throughout the extragranular layers of barrel cortex. In cases in which different tracers were injected in SII and MI, double-labeled neurons appeared above and below the layer IV septal compartment and at sites aligned with the boundaries of the layer IV barrels. To the extent that the columns of neurons aligned with the barrel and septal compartments represent functionally distinct circuits, these results indicate that SII receives information from both circuits, whereas MI receives inputs primarily from the septal circuits.