The cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1–4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico–basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

The cortico-basal ganglia-thalamic loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behavior, and the natural history of many neurological and neuropsychiatric diseases. Classically, the basal ganglia is conceptualized to contain three primary information output channels: motor, limbic, and associative. However, given the roughly 65 cortical areas and two dozen thalamic nuclei that feed into the dorsal striatum, a three-channel view is overly simplistic for explaining the myriad functions of the basal ganglia. Recent works from our lab and others have subdivided the dorsal striatum into numerous functional domains based on convergent and divergent inputs from the cortex and thalamus. To complete this work, we generated a comprehensive data pool of ∼700 injections placed across the striatum, external globus pallidus (GPe), substantia nigra pars reticulata (SNr), thalamic nuclei, and cortex. We identify 14 domains of SNr, 36 in the GPe, and 6 in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify 6 parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information with complex patterns of convergence and divergence through every elemental node of the entire cortico-basal ganglia loop. These experiments reveal multiple important novel features of the cortico-basal ganglia network motif. The prototypical sub-network structure is characterized by a highly interconnected nature, with cortical information processing through one or more striatal nodes, which send a convergent output to the SNr and a more parallelized output to the GPe; the GPe output then converges with the SNr. A domain of the thalamus receives the nigral output, and is interconnected with both the striatal domains and the cortical areas that filter into its nigral input source. This study provides conceptual advancement of our understanding of the structural and functional organization of the classic cortico-basal ganglia network.

The basolateral amygdalar complex (BLA) is implicated in behavioral processing ranging from fear acquisition to addiction. Newer methods like optogenetics have enabled the association of circuitspecific functionality to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. In this work, we applied computational analysis techniques to the results of our circuittracing experiments to create a foundational, comprehensive, multiscale connectivity atlas of the mouse BLA. The analyses identified three domains within the classically defined anterior BLA (BLAa) that house target-specific projection neurons with distinguishable cell body and dendritic morphologies. Further, we identify brain-wide targets of projection neurons located in the three BLAa domains as well as in the posterior BLA (BLAp), ventral BLA (BLAv), lateral (LA), and posterior basomedial (BMAp) nuclei. Projection neurons that provide input to each nucleus are also identifed. Functional characterization of some projection-defined BLA neurons were demonstrated via optogenetic and recording experiments. Hypotheses relating function to connection-defined BLA cell types are proposed. rACAd, Anterior cingulate cortical area, dorsal part, rostral region cACAd, Anterior cingulate cortical area, dorsal part, caudal region ACAv, Anterior cingulate cortical area, ventral part rACAv, Anterior cingulate cortical area, ventral part, rostral region cACAv, Anterior cingulate cortical area, ventral part, caudal region ACB, Nucleus accumbens AD, Anterodorsal nucleus of the thalamus ADP, Anterodorsal preoptic nucleus of the hypothalamus AHN, Anterior hypothalamic nucleus AI, Agranular insular cortical area AId, Agranular insular cortical area, dorsal part AIv, Agranular insular cortical area, ventral part AIv, Agranular insular cortical area, posterior part AM, Anteromedial nucleus of the thalamus AMd, Anteromedial nucleus of the thalamus, dorsal part AMv, Anteromedial nucleus of the thalamus, ventral part AON, Anterior olfactory nucleus AONm, Anterior olfactory nucleus, medial part AONpv, Anterior olfactory nucleus, posteroventral part ARH, Arcuate hypothalamic nucleus AUD, Auditory cortical area AUDd, Dorsal auditory cortical area AUDp, Primary auditory cortical area AUDv, Ventral auditory cortical area AV, Anteroventral nucleus of the thalamus AVP, Anteroventral preoptic nucleus AVPV, Anteroventral periventricular nucleus bic, Brachium of the inferior colliculus BLA, Basolateral amygdalar complex BLAa, Basolateral amygdalar nucleus, anterior part BLA.am, Basolateral amydalar nucleus, anterior part, medial domain BLA.al, Basolateral amydalar nucleus, anterior part, lateral domain BLA.ac, Basolateral amydalar nucleus, anterior part, caudal domain BLAp, Basolateral amygdalar nucleus, posterior part BLAv, Basolateral amygdalar nucleus, ventral part BMA, Basomedial amygdalar nucleus BMAa, Basomedial amygdalar nucleus, anterior part BMAp, Basomedial...

We report a case of a 63-year-old male who presented with synchronous pT1N1 p16-positive squamous cell carcinoma (SCC) of the left tonsil and pT4N0 p16-negative SCC of the left tongue.