Shubhodeep Chakrabarti

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. J. Comp. Neurol. 498:624–636, 2006.

Septal Columns in Rodent Barrel Cortex: Functional Circuits for Modulating Whisking Behavior

In rodents, each mystacial whisker is represented in the granular layer of primary somatosensory (SI) cortex by a compact cluster of cells known as a barrel, and barrels are separated from each other by domains that are called septa. Vertical columns of neurons aligned with each barrel act as a functional assembly to process information from a “principal” whisker, but a functional role has not been identified for vertical columns of neurons that are aligned with the septa. To determine whether these septal columns provide the main source of projections to primary motor (MI) cortex, we placed retrograde tracers in MI cortex and analyzed the location of the retrogradely labeled neurons with respect to the septal and barrel compartments of SI barrel cortex. In cases in which SI barrel cortex was sectioned tangentially, retrogradely labeled neurons in the extragranular layers of SI were plotted and superimposed onto reconstructions of the layer IV barrel field. In each of these cases, most labeled neurons were located above or below the septal regions of layer IV. When SI barrel cortex was sectioned coronally, we observed multiple columns of labeled SI neurons that were vertically aligned with the septal zones of layer IV. These results indicate that columns of neurons that are vertically aligned with the septa, or septal columns, are functionally linked by virtue of their projections to MI cortex. We hypothesize that these septal columns represent an interconnected and functionally distinct circuit that transmits information to MI and other brain regions involved in motor control. J. Comp. Neurol. 480:299–309, 2004.

Topography of cortical projections to the dorsolateral neostriatum in rats: multiple overlapping sensorimotor pathways.

In rodents, the whisker representation in primary somatosensory (SI) cortex projects to the dorsolateral neostriatum, but the location of these projections has never been characterized with respect to layer IV barrels and their intervening septa. To address this issue, we injected a retrograde tracer into the dorsolateral neostriatum and then reconstructed the location of the labeled corticostriatal neurons with respect to the cytochrome oxidase (CO)‐labeled barrels in SI. When the tracer was restricted to a small focal site in the neostriatum, the retrogradely labeled neurons formed elongated strips that were parallel to the curvilinear orientation of layer IV barrel rows. After larger tracer injections, labeled neurons were distributed uniformly across layer V and were aligned with both the barrel and septal compartments. Labeled projections from the contralateral SI barrel cortex, however, were much fewer in number and were disproportionately associated with the septal compartments. A comparison of the labeling patterns in the ipsilateral and contralateral hemispheres revealed symmetric, mirror‐image distributions that extended across primary motor cortex (MI) and multiple somatosensory cortical regions, including the secondary somatosensory (SII) cortex, the parietal ventral (PV) and parietal rhinal (PR) areas, and the posteromedial (PM) region. Examination of the thalamus revealed labeled neurons in the intralaminar nuclei, in the medial part of the posterior nucleus (POm), and in the ventrobasal complex. These results indicate that the dorsolateral neostriatum integrates sensorimotor information from multiple sensorimotor representations in the thalamus and cortex. J. Comp. Neurol. 499:33–48, 2006.

MI Neuronal Responses to Peripheral Whisker Stimulation: Relationship to Neuronal Activity in SI Barrels and Septa

The whisker region in the rodent primary motor (MI) cortex receives dense projections from neurons aligned with the layer IV septa in the whisker region of the primary somatosensory (SI) cortex. To compare whisker-induced responses in MI with respect to the SI responses in the septa and adjoining barrel regions, we used several experimental approaches in anesthetized rats. Reversible inactivation of SI and the surrounding cortex suppressed the magnitude of whisker-induced responses in the MI whisker region by 80%. Subsequent laminar analysis of MI responses to electrical or mechanical stimulation of the whisker pad revealed that the most responsive MI neurons were located >or=1.0 mm below the pia. When layer IV neurons in SI were recorded simultaneously with deep MI neurons during low-frequency (2-Hz) deflections of the whiskers, the neurons in the SI barrels responded 2-6 ms earlier than those in MI. Barrel neurons displayed similar response latencies at all stimulus frequencies, but the response latencies in MI and the SI septa increased significantly when the whiskers were deflected at frequencies of 8 Hz. Finally, cross-correlation analysis of neuronal activity in SI and MI revealed greater amounts of time-locked coordination among septa-MI neuron pairs than among barrel-MI neuron pairs. These results suggest that the somatosensory corticocortical inputs to MI cortex convey information processed by the SI septal circuits.

Differential response patterns in the si barrel and septal compartments during mechanical whisker stimulation.

A growing body of evidence suggests that the barrel and septal regions in layer IV of rat primary somatosensory (SI) cortex may represent separate processing channels. To assess this view, pairs of barrel and septal neurons were recorded simultaneously in the anesthetized rat while a 4x4 array of 16 whiskers was mechanically stimulated at 4, 8, 12, and 16 Hz. Compared with barrel neurons, regular-spiking septal neurons displayed greater increases in response latencies as the frequency of whisker stimulation increased. Cross-correlation analysis indicated that the incidence and strength of neuronal coordination varied with the relative spatial configuration (within vs. across rows) and compartmental location (barrel vs. septa) of the recorded neurons. Barrel and septal neurons were strongly coordinated if both neurons were in close proximity and resided in the same row. Some barrel neurons were weakly coordinated, but only if they resided in the same row. By contrast, the strength of coordination among pairs of septal neurons did not vary with their spatial proximity or their spatial configuration within the arcs and rows of the barrel field. These differential responses provide further support for the view that the barrel and septal regions represent the cortical gateway for processing streams that encode specific aspects of the sensorimotor information associated with whisking behavior.

Corticofugal projection patterns of whisker sensorimotor cortex to the sensory trigeminal nuclei

The primary (S1) and secondary (S2) somatosensory cortices project to several trigeminal sensory nuclei. One putative function of these corticofugal projections is the gating of sensory transmission through the trigeminal principal nucleus (Pr5), and some have proposed that S1 and S2 project differentially to the spinal trigeminal subnuclei, which have inhibitory circuits that could inhibit or disinhibit the output projections of Pr5. Very little, however, is known about the origin of sensorimotor corticofugal projections and their patterns of termination in the various trigeminal nuclei. We addressed this issue by injecting anterograde tracers in S1, S2 and primary motor (M1) cortices, and quantitatively characterizing the distribution of labeled terminals within the entire rostro-caudal chain of trigeminal sub-nuclei. We confirmed our anterograde tracing results by injecting retrograde tracers at various rostro-caudal levels within the trigeminal sensory nuclei to determine the position of retrogradely labeled cortical cells with respect to S1 barrel cortex. Our results demonstrate that S1 and S2 projections terminate in largely overlapping regions but show some significant differences. Whereas S1 projection terminals tend to cluster within the principal trigeminal (Pr5), caudal spinal trigeminal interpolaris (Sp5ic), and the dorsal spinal trigeminal caudalis (Sp5c), S2 projection terminals are distributed in a continuum across all trigeminal nuclei. Contrary to the view that sensory gating could be mediated by differential activation of inhibitory interconnections between the spinal trigeminal subnuclei, we observed that projections from S1 and S2 are largely overlapping in these subnuclei despite the differences noted earlier.

Streamlined sensory motor communication through cortical reciprocal connectivity in a visually guided eye movement task

Cortical computation is distributed across multiple areas of the cortex by networks of reciprocal connectivity. However, how such connectivity contributes to the communication between the connected areas is not clear. In this study, we examine the communication between sensory and motor cortices. We develop an eye movement task in mice and combine it with optogenetic suppression and two-photon calcium imaging techniques. We identify a small region in the secondary motor cortex (MOs) that controls eye movements and reciprocally connects with a rostrolateral part of the higher visual areas (VRL/A/AL). These two regions encode both motor signals and visual information; however, the information flow between the regions depends on the direction of the connectivity: motor information is conveyed preferentially from the MOs to the VRL/A/AL, and sensory information is transferred primarily in the opposite direction. We propose that reciprocal connectivity streamlines information flow, enhancing the computational capacity of a distributed network.Reciprocal connectivity enables tightly coupled information processing across cortical areas. Here the authors develop a visual oculomotor task in mice, identify a small motor area required for it, and demonstrate selective exchange of sensory and motor information between the motor and sensory areas.

Studying motor cortex function using the rodent vibrissal system

The function of the mammalian motor cortex was one of the first problems studied in neuroscience. But until today, the major principles of the workings of the motor cortex have remained conjectural. It is clear that motor cortex holds a topographic map of body parts. But does that mean that the motor cortex itself is undertaking the challenging task of converting motor plans (i.e., intended trajectories and effects of actions) into low level motor commands appropriate to drive the muscles? Work of many decades on motor function has revealed the existence of dedicated networks, the so-called central pattern generators (CPGs). Many, if not all of these CPGs, are located subcortically and are likely to be involved in the translation of motor plans into actual muscle contractions. Unfortunately the detailed circuitry and cellular elements of CPGs are only vaguely known. More recent work has elucidated continuous as well as discontinuous (discrete) mapping of the motor cortex to movement. For the quest of understanding motor cortex–CPG interactions, discontinuities are important because they allow us to dissect how neighboring motor cortex sites connect to different CPGs for different purposes—but driving the very same muscles. The rodent whisker motor system is a decidedly modular system. Neighboring cortical areas drive very distinct whisker movements used by the animals in different contexts. We argue that the modularity of the whisker system together with its great accessibility is promising to establish a model system for the interactions of the motor cortex and CPGs on the cellular and network levels and, thus, will also be of high value in understanding the more complex and continuously organized motor cortex of the arm/hand/finger system in primates.

Whisking Control by Motor Cortex

The rodent whiskers (the so-called vibrissae) are an active scanning sensorimotor system with major perceptual functions. Apart from tactile perception, the whisker motor system also has important contributions to the animals’ navigation and orientation capabilities. The whisker motor system is highly modular with circuits processing basic motor commands, rhythmic whisking, and modulating the motor actions using information from incoming tactile signals. The vibrissal primary motor cortex (vM1) reflects these functional divisions by displaying a distinct set of sub-areas with different functions. Like the primate fingertip system, vM1 displays direct cortico-motoneurons (CM) cells, in principle compatible with the notion that vM1 is involved in directly computing patterns of muscle activity. There is strong evidence, however, that vM1 action on the muscles is rather indirect with important brainstem premotor networks bearing the responsibility of computing muscle activity patterns. The connectivity of the different vM1 modules to central pattern generators (CPGs), generating the basic rhythmic movement patterns and the trigeminal brainstem loop (TBL), the brainstem sensorimotor reflex arc, representing the lowest hierarchy of sensorimotor interactions, are being unearthed by current investigations.

The Rodent Vibrissal System as a Model to Study Motor Cortex Function

The function of mammalian motor cortex was one of the first problems studied in neuroscience. But until today, the major principles of the workings of motor cortex have remained conjectural. It is clear that motor cortex holds a topographic map of body parts. However, does that necessarily imply that motor cortex itself undertakes the challenging task of converting movement plans (i.e. intended trajectories and effects of actions) into low level motor commands appropriate for driving the muscles? Many decades of research on motor function has shown that this is not entirely true by revealing the existence of dedicated networks, the so-called central pattern generators (CPGs) . Many, if not all of them, are located sub-cortically, and are likely to take over this task. Unfortunately the detailed circuitry and cellular elements of CPGs are only vaguely known. More recent work has elucidated continuous as well as discontinuous (discrete) mapping of motor cortex to movement. In the quest to understand motor cortex-CPG interactions, discontinuities are important because they allow us to dissect how neighboring motor cortex sites connect to different CPGs for different purposes—driving the very same muscles. The rodent whisker motor system is a decidedly modular system. Neighboring cortical areas drive very distinct whisker movements used by the animals in different contexts. We review the state of art in this system and argue that the modularity of the whisker system together with its great accessibility makes it a promising candidate for a model system for the investigation of motor cortex—CPG interactions on the cellular and network level—a highly valuable tool for the subsequent understanding of the more complex and continuously organized motor cortex of the arm/hand/finger system in primates.