Retrosplenial inputs drive visual representations in the medial entorhinal cortex.

The importance of visual cues for navigation and goal-directed behavior is well established, although the neural mechanisms supporting sensory representations in navigational circuits are largely unknown. Navigation is fundamentally dependent on the medial entorhinal cortex (MEC), which receives direct projections from neocortical visual areas, including the retrosplenial cortex (RSC). Here, we perform high-density recordings of MEC neurons in awake, head-fixed mice presented with simple visual stimuli and assess the dynamics of sensory-evoked activity.

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.

Retrosplenial inputs drive diverse visual representations in the medial entorhinal cortex.

The ability of rodents to use visual cues for successful navigation and goal-directed behavior has been long appreciated, although the neural mechanisms supporting sensory representations in navigational circuits are largely unknown. Navigation is fundamentally dependent on the hippocampus and closely connected entorhinal cortex, whose neurons exhibit characteristic firing patterns corresponding to the animal's location. The medial entorhinal cortex (MEC) receives direct projections from sensory areas in the neocortex, suggesting the ability to encode sensory information.

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.

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.

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.

NMDAR-Dependent Emergence of Behavioral Representation in Primary Visual Cortex.

Although neocortical sensory areas are generally thought to faithfully represent external stimuli, cortical networks exhibit considerable functional plasticity, allowing them to modify their output to reflect ongoing behavioral demands. We apply longitudinal 2-photon imaging of activity in the primary visual cortex (V1) of mice learning a conditioned eyeblink task to investigate the dynamic representations of task-relevant information. We find that, although all V1 neurons robustly and stably encode visual input, pyramidal cells and parvalbumin-expressing interneurons exhibit experience-dependent emergence of accurate behavioral representations during learning.

Diverse Spatiotemporal Scales of Cholinergic Signaling in the Neocortex.

ACh is a signaling molecule in the mammalian CNS, with well-documented influence over cognition and behavior. However, the nature of cholinergic signaling in the brain remains controversial, with ongoing debates focused on the spatial and temporal resolution of ACh activity. Generally, opposing views have embraced a dichotomy between transmission as slow and volume-mediated versus fast and synaptic.

Layer 5 Circuits in V1 Differentially Control Visuomotor Behavior.

Neocortical sensory areas are thought to act as distribution hubs, transmitting information about the external environment to downstream areas. Within primary visual cortex, various populations of pyramidal neurons (PNs) send axonal projections to distinct targets, suggesting multiple cellular networks may be independently engaged during behavior. We investigated whether PN subpopulations differentially support visual detection by training mice on a novel eyeblink conditioning task.

Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism.

Ketamine disrupts neuromodulatory control of glutamatergic synaptic transmission.

A growing body of literature has demonstrated the potential for ketamine in the treatment of major depression. Sub-anesthetic doses produce rapid and sustained changes in depressive behavior, both in patients and rodent models, associated with reorganization of glutamatergic synapses in the prefrontal cortex (PFC). While ketamine is known to regulate N-methyl-D-aspartate (NMDA) -type glutamate receptors (NMDARs), the full complement of downstream cellular consequences for ketamine administration are not well understood.

Preserving the balance: diverse forms of long-term GABAergic synaptic plasticity.

Cellular mechanisms that regulate the interplay of synaptic excitation and inhibition are thought to be central to the functional stability of healthy neuronal circuits. A growing body of literature demonstrates the capacity for inhibitory GABAergic synapses to exhibit long-term plasticity in response to changes in neuronal activity. Here, we review this expanding field of research, focusing on the diversity of mechanisms that link glutamatergic signalling, postsynaptic action potentials and inhibitory synaptic strength.

Potassium channels contribute to activity-dependent regulation of dendritic inhibition.

GABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood.

Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition.

Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition.

Millisecond precision temporal encoding of stimulus features during cortically generated gamma oscillations in the rat somatosensory cortex.

Key Points: Rodents explore their immediate environment using their whiskers. Such exploration leads to micromotions, which contain many high-frequency (50-200 Hz) components. High-frequency whisker motion is represented faithfully in the temporal structure of the spike trains of trigeminal neurons.

Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits.

GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation.

Disruption of Coordinated Presynaptic and Postsynaptic Maturation Underlies the Defects in Hippocampal Synapse Stability and Plasticity in Abl2/Arg-Deficient Mice.

Unlabelled: Immature glutamatergic synapses in cultured neurons contain high-release probability (Pr) presynaptic sites coupled to postsynaptic sites bearing GluN2B-containing NMDA receptors (NMDARs), which mature into low-Pr, GluN2B-deficient synapses. Whether this coordinated maturation of high-Pr, GluN2B(+) synapses to low-Pr, GluN2B-deficient synapses actually occurs in vivo, and if so, what factors regulate it and what role it might play in long-term synapse function and plasticity are unknown. We report that loss of the integrin-regulated Abl2/Arg kinase in vivo yields a subpopulation of "immature" high-Pr, GluN2B(+) hippocampal synapses that are maintained throughout late postnatal development and early adulthood.

Visual Deprivation During the Critical Period Enhances Layer 2/3 GABAergic Inhibition in Mouse V1.

Unlabelled: The role of GABAergic signaling in establishing a critical period for experience in visual cortex is well understood. However, the effects of early experience on GABAergic synapses themselves are less clear. Here, we show that monocular deprivation (MD) during the adolescent critical period produces marked enhancement of GABAergic signaling in layer 2/3 of mouse monocular visual cortex.

Projection-Specific Visual Feature Encoding by Layer 5 Cortical Subnetworks.

Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives a distinct version of sensory information. We used in vivo calcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex.