Functions of the neocortex depend on its bidirectional communication with the thalamus, via cortico-thalamo-cortical (CTC) loops. Recent work dissecting the synaptic connectivity in these loops is ...generating a clearer picture of their cellular organization. Here, we review findings across sensory, motor and cognitive areas, focusing on patterns of cell type-specific synaptic connections between the major types of cortical and thalamic neurons. We outline simple and complex CTC loops, and note features of these loops that appear to be general versus specialized. CTC loops are tightly interlinked with local cortical and corticocortical (CC) circuits, forming extended chains of loops that are probably critical for communication across hierarchically organized cerebral networks. Such CTC-CC loop chains appear to constitute a modular unit of organization, serving as scaffolding for area-specific structural and functional modifications. Inhibitory neurons and circuits are embedded throughout CTC loops, shaping the flow of excitation. We consider recent findings in the context of established CTC and CC circuit models, and highlight current efforts to pinpoint cell type-specific mechanisms in CTC loops involved in consciousness and perception. As pieces of the connectivity puzzle fall increasingly into place, this knowledge can guide further efforts to understand structure-function relationships in CTC loops.
Corticostriatal projections are essential components of forebrain circuits and are widely involved in motivated behaviour. These axonal projections are formed by two distinct classes of cortical ...neurons, intratelencephalic (IT) and pyramidal tract (PT) neurons. Convergent evidence points to IT versus PT differentiation of the corticostriatal system at all levels of functional organization, from cellular signalling mechanisms to circuit topology. There is also growing evidence for IT/PT imbalance as an aetiological factor in neurodevelopmental, neuropsychiatric and movement disorders - autism, amyotrophic lateral sclerosis, obsessive-compulsive disorder, schizophrenia, Huntington's and Parkinson's diseases and major depression are highlighted here.
Similarities in neocortical circuit organization across areas and species suggest a common strategy to process diverse types of information, including sensation from diverse modalities, motor control ...and higher cognitive processes. Cortical neurons belong to a small number of main classes. The properties of these classes, including their local and long-range connectivity, developmental history, gene expression, intrinsic physiology and in vivo activity patterns, are remarkably similar across areas. Each class contains subclasses; for a rapidly growing number of these, conserved patterns of input and output connections are also becoming evident. The ensemble of circuit connections constitutes a basic circuit pattern that appears to be repeated across neocortical areas, with area- and species-specific modifications. Such 'serially homologous' organization may adapt individual neocortical regions to the type of information each must process.
Rodents move their whiskers to locate and identify objects. Cortical areas involved in vibrissal somatosensation and sensorimotor integration include the vibrissal area of the primary motor cortex ...(vM1), primary somatosensory cortex (vS1; barrel cortex), and secondary somatosensory cortex (S2). We mapped local excitatory pathways in each area across all cortical layers using glutamate uncaging and laser scanning photostimulation. We analyzed these maps to derive laminar connectivity matrices describing the average strengths of pathways between individual neurons in different layers and between entire cortical layers. In vM1, the strongest projection was L2/3→L5. In vS1, strong projections were L2/3→L5 and L4→L3. L6 input and output were weak in both areas. In S2, L2/3→L5 exceeded the strength of the ascending L4→L3 projection, and local input to L6 was prominent. The most conserved pathways were L2/3→L5, and the most variable were L4→L2/3 and pathways involving L6. Local excitatory circuits in different cortical areas are organized around a prominent descending pathway from L2/3→L5, suggesting that sensory cortices are elaborations on a basic motor cortex-like plan.
Hippocampus, granular retrosplenial cortex (RSCg), and anterior thalamic nuclei (ATN) interact to mediate diverse cognitive functions. To identify cellular mechanisms underlying ...hippocampo-thalamo-retrosplenial interactions, we investigated the potential circuit suggested by projections to RSCg layer 1 (L1) from GABAergic CA1 neurons and ATN. We find that CA1→RSCg projections stem from GABAergic neurons with a distinct morphology, electrophysiology, and molecular profile. Their long-range axons inhibit L5 pyramidal neurons in RSCg via potent synapses onto apical tuft dendrites in L1. These inhibitory inputs intercept L1-targeting thalamocortical excitatory inputs from ATN to coregulate RSCg activity. Subicular axons, in contrast, excite proximal dendrites in deeper layers. Short-term plasticity differs at each connection. Chemogenetically abrogating CA1→RSCg or ATN→RSCg connections oppositely affects the encoding of contextual fear memory. Our findings establish retrosplenial-projecting CA1 neurons as a distinct class of long-range dendrite-targeting GABAergic neuron and delineate an unusual cortical circuit specialized for integrating long-range inhibition and thalamocortical excitation.
Excitatory synaptic projections to layer 2/3 (L2/3) pyramidal neurons in brain slices from the rat barrel cortex were measured using quantitative laser-scanning photostimulation (LSPS) mapping. In ...the barrel cortex, cytoarchitectonic "barrels" and "septa" in L4 define a stereotypical array of landmarks, allowing alignment and averaging of LSPS maps from multiple cells in different slices. We distinguished inputs to L2 and L3 neurons above barrels and septa. Average input maps revealed that barrel-related ascending projections (L4-->2/3barrel) interdigitated with a novel septum-related projection (L5A-->2septum). We also explored the functional organization of these projections by comparing the input maps of multiple cells in individual slices. L2/3 cells sharing the same barrel-related column showed strong correlations in their input maps, independent of their precise locations within the column; otherwise, correlations fell rapidly as a function of intersomatic separation. Our data indicate that barrel-related and septum-related columns are associated with distinct functional circuits. These projections are likely to mediate parallel processing of somatosensory signals within the barrel cortex, with L4-->2/3barrel and L5A-->2septum representing the intracortical continuations of, respectively, the subcortical lemniscal and paralemniscal systems conveying somatosensory information to the barrel cortex.
Determining how long-range synaptic inputs engage pyramidal neurons in primary motor cortex (M1) is important for understanding circuit mechanisms involved in regulating movement. We used ...channelrhodopsin-2-assisted circuit mapping to characterize the long-range excitatory synaptic connections made by multiple cortical and thalamic areas onto pyramidal neurons in mouse vibrissal motor cortex (vM1). Each projection innervated vM1 pyramidal neurons with a unique laminar profile. Collectively, the profiles for different sources of input partially overlapped and spanned all cortical layers. Specifically, orbital cortex (OC) inputs primarily targeted neurons in L6. Secondary motor cortex (M2) inputs excited neurons mainly in L5B, including pyramidal tract neurons. In contrast, thalamocortical inputs from anterior motor-related thalamic regions, including VA/VL (ventral anterior thalamic nucleus/ventrolateral thalamic nucleus), targeted neurons in L2/3 through L5B, but avoided L6. Inputs from posterior sensory-related thalamic areas, including POm (posterior thalamic nuclear group), targeted neurons only in the upper layers (L2/3 and L5A), similar to inputs from somatosensory (barrel) cortex. Our results show that long-range excitatory inputs target vM1 pyramidal neurons in a layer-specific manner. Inputs from sensory-related cortical and thalamic areas preferentially target the upper-layer pyramidal neurons in vM1. In contrast, inputs from OC and M2, areas associated with volitional and cognitive aspects of movements, bypass local circuitry and have direct monosynaptic access to neurons projecting to brainstem and thalamus.
Corticospinal pyramidal neurons mediate diverse aspects of motor behavior. We measured spike-related electrophysiological properties of identified corticospinal neurons in primary motor cortex slices ...from young adult mice. Several consistent features were observed in the suprathreshold responses to current steps: 1) Corticospinal neurons fired relatively fast action potentials (APs; width at half-maximum 0.65 ± 0.13 ms, mean ± standard deviation SD) compared with neighboring callosally projecting corticostriatal neurons. Corticospinal AP width was intermediate between 2 classes of inhibitory interneuron in layer 5B. Spike-to-spike variability in AP width and other spike waveform parameters was low, even during repetitive firing up to 20 Hz, that is, the relative narrowness of corticospinal APs was essentially frequency independent. 2) Frequency-current (f-I) relationships were nearly linear. 3) Trains of APs displayed regular firing, with rates typically staying constant or accelerating over time. Corticospinal neurons recorded from older mice (up to 4 months) or from a separate lateral cortical area (Region B; corresponding to secondary somatosensory cortex) showed generally similar intrinsic properties. Our findings have implications for interpreting spike waveforms of in vivo recorded neurons in the motor cortex. This analysis provides a framework for further biophysical and computational investigations of corticospinal neurons and their roles in motor cortical function.
Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs ...from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2-6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control.
Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the "map") to sensorimotor networks involved the control of movement (the "motor").
The Wind Imaging Interferometer (WINDII) was launched on the NASA's Upper Atmosphere Research Satellite on 12 September 1991 and operated until 2003. Its role in the mission was to measure vector ...winds in the Earth's atmosphere from 80 to 110 km, but its measurements extended to nearly 300 km. The approach employed was to measure Doppler shifts from a suite of visible region airglow lines emitted over this altitude range. These included atomic oxygen O(1S) and O(1D) lines, as well as lines in the OH Meinel (8,3) and O2 Atmospheric (0,0) bands. The instrument employed was a Doppler Michelson Interferometer that measured the Doppler shift as a phase shift of the cosinusoidal interferogram generated by single airglow lines. An extensive validation program was conducted after launch to confirm the accuracy of the measurements. The dominant wind field, the first one observed by WINDII, was that of the migrating diurnal tide at the equator. The overall most notable WINDII contribution followed from this: determining the influence of dynamics on the transport of atmospheric species. Currently, nonmigrating tides are being studied in the thermosphere at both equatorial and high latitudes. Other aspects investigated included solar and geomagnetic influences, temperatures from atmospheric‐scale heights, nitric oxide concentrations, and the occurrence of polar mesospheric clouds. The results of these observations are reviewed from a perspective of 20 years. A future perspective is then projected, involving more recently developed concepts. It is intended that this description will be helpful for those planning future missions.
Key Points
Doppler Michelson interferometers excel in atmospheric space wind measurements
Upper atmosphere winds dramatically influence atomic oxygen concentrations
The thermosphere has enormous scope for future atmospheric dynamics measurements
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