The autophagy inhibitor NSC185058 suppresses mTORC1-mediated protein anabolism in cultured skeletal muscle.

The mammalian target of rapamycin (mTOR), and specifically the mTOR complex 1 (mTORC1) is the central regulator of anabolism in skeletal muscle. Among the many functions of this kinase complex is the inhibition of the catabolic process of autophagy; however, less work has been done in investigating the role of autophagy in regulating mTORC1 signaling. Using an in vitro model to better understand the pathways involved, we activated mTORC1 by several different means (growth factors, leucine supplementation, or muscle contraction), alone or with the autophagy inhibitor NSC185058.

Developmental trajectory of cortical somatostatin interneuron function.

GABAergic inhibition is critical to the proper development of neocortical circuits. However, GABAergic interneurons are highly diverse and the developmental roles of distinct inhibitory subpopulations remain largely unclear. Dendrite-targeting, somatostatin-expressing interneurons (SST-INs) in the mature cortex regulate synaptic integration and plasticity in excitatory pyramidal neurons (PNs) and exhibit unique feature selectivity.

Traumatic brain injury disrupts state-dependent functional cortical connectivity in a mouse model.

Traumatic brain injury (TBI) is the leading cause of death in young people and can cause cognitive and motor dysfunction and disruptions in functional connectivity between brain regions. In human TBI patients and rodent models of TBI, functional connectivity is decreased after injury. Recovery of connectivity after TBI is associated with improved cognition and memory, suggesting an important link between connectivity and functional outcome.

The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo.

Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective.

Rapid fluctuations in functional connectivity of cortical networks encode spontaneous behavior.

Experimental work across species has demonstrated that spontaneously generated behaviors are robustly coupled to variations in neural activity within the cerebral cortex. Functional magnetic resonance imaging data suggest that temporal correlations in cortical networks vary across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these data generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior observed in awake animals.

Transthalamic input to higher-order cortex selectively conveys state information.

Communication among different neocortical areas is largely thought to be mediated by long-range synaptic interactions between cortical neurons, with the thalamus providing only an initial relay of information from the sensory periphery. Higher-order thalamic nuclei receive strong synaptic inputs from the cortex and send robust projections back to other cortical areas, providing a distinct and potentially critical route for cortico-cortical communication. However, the relative contributions of corticocortical and thalamocortical inputs to higher-order cortical function remain unclear.

Beyond rhythm - a framework for understanding the frequency spectrum of neural activity.

Cognitive and behavioral processes are often accompanied by changes within well-defined frequency bands of the local field potential (LFP i.e., the voltage induced by neuronal activity).

VIP interneurons regulate cortical size tuning and visual perception.

Cortical circuit function is regulated by extensively interconnected, diverse populations of GABAergic interneurons that may play key roles in shaping circuit operation according to behavioral context. A specialized population of interneurons that co-express vasoactive intestinal peptides (VIP-INs) are activated during arousal and innervate other INs and pyramidal neurons (PNs). Although state-dependent modulation of VIP-INs has been extensively studied, their role in regulating sensory processing is less well understood.

Continuous glucose monitoring in a healthy population: understanding the post-prandial glycemic response in individuals without diabetes mellitus.

Continuous glucose monitoring has become a common adjunct in the management of Diabetes Mellitus. However, there has been a recent trend among individuals without diabetes using these devices as a means of monitoring their health. The increased visibility of glucose data has allowed users to study the effect lifestyle has upon post-prandial glucose levels.

Beyond rhythm - A framework for understanding the frequency spectrum of neural activity.

Cognitive and behavioral processes are often accompanied by changes within well-defined frequency bands of the local field potential (LFP i.e., the voltage induced by neuronal activity).

VIP interneurons regulate cortical size tuning and visual perception.

Local cortical circuit function is regulated by diverse populations of GABAergic interneurons with distinct properties and extensive interconnectivity. Inhibitory-to-inhibitory interactions between interneuron populations may play key roles in shaping circuit operation according to behavioral context. A specialized population of GABAergic interneurons that co-express vasoactive intestinal peptide (VIP-INs) are activated during arousal and locomotion and innervate other local interneurons and pyramidal neurons.

Developmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics.

GABAergic inhibition plays an important role in the establishment and maintenance of cortical circuits during development. Neuregulin 1 (Nrg1) and its interneuron-specific receptor ErbB4 are key elements of a signaling pathway critical for the maturation and proper synaptic connectivity of interneurons. Using conditional deletions of the ERBB4 gene in mice, we tested the role of this signaling pathway at two developmental timepoints in parvalbumin-expressing (PV) interneurons, the largest subpopulation of cortical GABAergic cells.

Putting the brakes on synchrony: VIP interneurons tune visually evoked rhythmic activity.

Visually evoked synchrony in the primary visual cortex has proven to be a robust model for examining circuit interactions. In this issue of Neuron, Veit et al. highlight a previously unappreciated role for VIP interneurons in regulating local and long-range patterns of coordinated neural activity.

Spatiotemporally heterogeneous coordination of cholinergic and neocortical activity.

Variation in an animal's behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent circuit dynamics may reflect neuromodulatory influences such as that of acetylcholine (ACh). Although early literature suggested that ACh exerts broad, homogeneous control over cortical function, recent evidence indicates potential anatomical and functional segregation of cholinergic signaling.

Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types.

Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between targeted cell populations. However, current indicators lack the requisite sensitivity for in vivo multipopulation imaging. We describe next-generation green and red voltage sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants pAce and pAceR.

Spatiotemporal dynamics in large-scale cortical networks.

Investigating links between nervous system function and behavior requires monitoring neuronal activity at a range of spatial and temporal scales. Here, we summarize recent progress in applying two distinct but complementary approaches to the study of network dynamics in the neocortex. Mesoscopic calcium imaging allows simultaneous monitoring of activity across most of the cortex at moderate spatiotemporal resolution.

The Logic of Developing Neocortical Circuits in Health and Disease.

The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition.

Simultaneous cortex-wide fluorescence Ca imaging and whole-brain fMRI.

Achieving a comprehensive understanding of brain function requires multiple imaging modalities with complementary strengths. We present an approach for concurrent widefield optical and functional magnetic resonance imaging. By merging these modalities, we can simultaneously acquire whole-brain blood-oxygen-level-dependent (BOLD) and whole-cortex calcium-sensitive fluorescent measures of brain activity.

Mesoscopic Imaging: Shining a Wide Light on Large-Scale Neural Dynamics.

Optical imaging has revolutionized our ability to monitor brain activity, spanning spatial scales from synapses to cells to circuits. Here, we summarize the rapid development and application of mesoscopic imaging, a widefield fluorescence-based approach that balances high spatiotemporal resolution with extraordinarily large fields of view. By leveraging the continued expansion of fluorescent reporters for neuronal activity and novel strategies for indicator expression, mesoscopic analysis enables measurement and correlation of network dynamics with behavioral state and task performance.

Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior.

Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene . Mutations of that are restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potential key point of vulnerability in neurodevelopmental disorders.

Mechanisms underlying gain modulation in the cortex.

Cortical gain regulation allows neurons to respond adaptively to changing inputs. Neural gain is modulated by internal and external influences, including attentional and arousal states, motor activity and neuromodulatory input. These influences converge to a common set of mechanisms for gain modulation, including GABAergic inhibition, synaptically driven fluctuations in membrane potential, changes in cellular conductance and changes in other biophysical neural properties.

Activation of Distinct Channelrhodopsin Variants Engages Different Patterns of Network Activity.

Several recently developed Channelrhodopsin (ChR) variants are characterized by rapid kinetics and reduced desensitization in comparison to the widely used ChR2. However, little is known about how varying opsin properties may regulate their interaction with local network dynamics. We compared evoked cortical activity in mice expressing three ChR variants with distinct temporal profiles under the CamKII promoter: Chronos, Chrimson, and ChR2.

Up and Down States of Cortical Neurons in Focal Limbic Seizures.

Recent work suggests an important role for cortical-subcortical networks in seizure-related loss of consciousness. Temporal lobe seizures disrupt subcortical arousal systems, which may lead to depressed cortical function and loss of consciousness. Extracellular recordings show ictal neocortical slow waves at about 1 Hz, but it is not known whether these simply represent seizure propagation or alternatively deep sleep-like activity, which should include cortical neuronal Up and Down states.