Electrocorticography reveals thalamic control of cortical dynamics following traumatic brain injury

The return of consciousness after traumatic brain injury (TBI) is associated with restoring complex cortical dynamics; however, it is unclear what interactions govern these complex dynamics. Here, we set out to uncover the mechanism underlying the return of consciousness by measuring local field potentials (LFP) using invasive electrophysiological recordings in patients recovering from TBI. We found that injury to the thalamus, and its efferent projections, on MRI were associated with repetitive and low complexity LFP signals from a highly structured phase space, resembling a low-dimensional ring attractor. But why do thalamic injuries in TBI patients result in a cortical attractor? We built a simplified thalamocortical model, which connotes that thalamic input facilitates the formation of cortical ensembles required for the return of cognitive function and the content of consciousness. These observations collectively support the view that thalamic input to the cortex enables rich cortical dynamics associated with consciousness.

Understanding Emotions: Origins and Roles of the Amygdala

Emotions arise from activations of specialized neuronal populations in several parts of the cerebral cortex, notably the anterior cingulate, insula, ventromedial prefrontal, and subcortical structures, such as the amygdala, ventral striatum, putamen, caudate nucleus, and ventral tegmental area. Feelings are conscious, emotional experiences of these activations that contribute to neuronal networks mediating thoughts, language, and behavior, thus enhancing the ability to predict, learn, and reappraise stimuli and situations in the environment based on previous experiences. Contemporary theories of emotion converge around the key role of the amygdala as the central subcortical emotional brain structure that constantly evaluates and integrates a variety of sensory information from the surroundings and assigns them appropriate values of emotional dimensions, such as valence, intensity, and approachability. The amygdala participates in the regulation of autonomic and endocrine functions, decision-making and adaptations of instinctive and motivational behaviors to changes in the environment through implicit associative learning, changes in short- and long-term synaptic plasticity, and activation of the fight-or-flight response via efferent projections from its central nucleus to cortical and subcortical structures.

Neuroanatomical organization and functional roles of PVN MC4R pathways in physiological and behavioral regulations

ABSTRACTObjectiveThe paraventricular nucleus of hypothalamus (PVN) is an integrative center in the brain orchestrating a wide range of physiological and behavioral responses. While the PVN melanocortin 4 receptor (MC4R) signaling (PVNMC4R+) is undoubtedly involved in feeding regulation, the neuroanatomical organization of PVNMC4R+ pathway and its role in diverse physiological and behavioral regulations have not been fully understood. Here we aimed to better characterize the input-output organization of PVNMC4R+ neurons and further test their potential functional roles beyond feeding.MethodsUsing a combination of viral tools, we performed a comprehensive mapping of PVNMC4R+ circuits and tested the effects of chemogenetic activation of PVNMC4R+ neurons on thermogenesis, cardiovascular control and other behavioral regulations beyond feeding.ResultsWe found that PVNMC4R+ neurons broadly innervate many different brain regions known to be important not only for feeding but also for neuroendocrine and autonomic control of thermogenesis and cardiovascular function, including but not limited to preoptic area, median eminence, parabrachial nucleus, locus coeruleus, nucleus of solitary tract, ventrolateral medulla and thoracic spinal cord. Contrary to broad efferent projections, PVNMC4R+ neurons receive monosynaptic inputs from limited brain regions, including medial preoptic nucleus, arcuate and dorsomedial hypothalamic nuclei, and supraoptic nucleus. Consistent with broad efferent projections, chemogenetic activation of PVNMC4R+ neurons not only suppressed feeding but also led to an apparent increase in heart rate, blood pressure and brown adipose tissue thermogenesis. Strikingly, these physiological changes accompanied an unexpected repetitive bedding-removing behavior followed by hypoactivity and resting-like behavior.ConclusionsOur results clarify the neuroanatomical organization of PVNMC4R+ circuits and shed new light on the roles of PVNMC4R+ pathways in autonomic control of thermogenesis, cardiovascular function and other behavioral regulations.

Divergent pallidal pathways underlying distinct Parkinsonian behavioral deficits

The basal ganglia are a group of subcortical nuclei that regulates motor and cognitive functions1,2. Recent identification of neuronal heterogeneity in the basal ganglia suggests that functionally distinct neural circuits defined by their efferent projections exist even within the same nuclei3-5. This distinction may account for a multitude of symptoms associated with basal ganglia disorders such as Parkinson’s disease (PD)6,7. However, our incomplete understanding of the basal ganglia functional organization has hindered further investigation of individual circuits that may underlie different behavioral symptoms in disease states. Here we functionally define two distinct classes of parvalbumin-expressing neurons in the mouse external globus pallidus (GPe-PV) embedded within discrete neural pathways and establish their contributions to different Parkinsonian behavioral deficits. We find that GPe-PV neurons projecting to the substantia nigra pars reticulata (SNr) or parafascicular thalamus (PF) undergo different electrophysiological adaptations in response to dopamine depletion. Furthermore, counteracting these adaptations in each population can selectively alleviate movement deficits or behavioral inflexibility in a Parkinsonian mouse model. Our findings provide a novel framework to understand the circuit basis of separate behavioral symptoms in Parkinsonian state which could provide better strategies for the treatment of PD.

A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons

Among the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability. Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show that P2ry1-Pet1 DR neurons – the most molecularly distinct subtype – possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of Pet1 neuron subtypes.

Corticocortical Connections of the Rostral Forelimb Area in Rats: A Quantitative Tract-Tracing Study

The rostral forelimb area (RFA) in the rat is considered to be a premotor cortical region based primarily on its efferent projections to the primary motor cortex. The purpose of the present study was to identify corticocortical connections of RFA, and to describe the relative strength of connections with other cortical areas. This will allow us to better understand the broader cortical network in which RFA participates, and thus, determine its function in motor behavior. In the present study, the RFA of adult male Long-Evans rats (n=6) was identified using intracortical microstimulation techniques and injected with the tract tracer, biotinylated dextran amine (BDA). In post-mortem tissue, location of BDA-labeled terminal boutons and neuronal somata were plotted and superimposed on cortical field boundaries. The results demonstrated that the RFA has dense to moderate reciprocal connections with primary motor cortex, the frontal cortex medial and lateral to RFA, primary somatosensory cortex (S1), and lateral somatosensory areas. Importantly, S1 connections were dense to moderate in dysgranular zones, but sparse to negligible in granular zones. Cortical connections of RFA in rat are strikingly similar to cortical connections of the ventral premotor cortex in non-human primates, suggesting that these areas share similar functions.