Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing.

Astrocytes, which are increasingly recognized as pivotal constituents of brain circuits governing a wide range of functions, express GABA transporter 3 (Gat3), an astrocyte-specific GABA transporter responsible for maintenance of extra-synaptic GABA levels. Here, we examined the functional role of Gat3 in astrocyte-mediated modulation of neuronal activity and information encoding. First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice.

Cortical norepinephrine-astrocyte signaling critically mediates learned behavior.

Updating behavior based on feedback from the environment is a crucial means by which organisms learn and develop optimal behavioral strategies. Norepinephrine (NE) release from the locus coeruleus (LC) has been shown to mediate learned behaviors such that in a task with graded stimulus uncertainty and performance, a high level of NE released after an unexpected outcome causes improvement in subsequent behavior. Yet, how the transient activity of LC-NE neurons, lasting tens of milliseconds, influences behavior several seconds later, is unclear.

A paradigm for ethanol consumption in head-fixed mice during prefrontal cortical two-photon calcium imaging.

The prefrontal cortex (PFC) is a hub for cognitive behaviors and is a key target for neuroadaptations in alcohol use disorders. Recent advances in genetically encoded sensors and functional microscopy allow multimodal in vivo PFC activity recordings at subcellular and cellular scales. While these methods could enable a deeper understanding of the relationship between alcohol and PFC function/dysfunction, they typically require animals to be head-fixed.

Intrinsic forebrain arousal dynamics governs sensory stimulus encoding.

The neural encoding of sensory stimuli is subject to the brain's internal circuit dynamics. Recent work has demonstrated that the resting brain exhibits widespread, coordinated activity that plays out over multisecond timescales in the form of quasi-periodic spiking cascades. Here we demonstrate that these intrinsic dynamics persist during the presentation of visual stimuli and markedly influence the efficacy of feature encoding in the visual cortex.

A paradigm for ethanol consumption in head-fixed mice during prefrontal cortical two-photon calcium imaging.

The prefrontal cortex (PFC) is a hub for higher-level cognitive behaviors and is a key target for neuroadaptations in alcohol use disorders. Preclinical models of ethanol consumption are instrumental for understanding how acute and repeated drinking affects PFC structure and function. Recent advances in genetically encoded sensors of neuronal activity and neuromodulator release combined with functional microscopy (multiphoton and one-photon widefield imaging) allow multimodal PFC recordings at subcellular and cellular scales.

Astrocyte glutamate uptake coordinates experience-dependent, eye-specific refinement in developing visual cortex.

The uptake of glutamate by astrocytes actively shapes synaptic transmission, however its role in the development and plasticity of neuronal circuits remains poorly understood. The astrocytic glutamate transporter, GLT1 is the predominant source of glutamate clearance in the adult mouse cortex. Here, we examined the structural and functional development of the visual cortex in GLT1 heterozygous (HET) mice using two-photon microscopy, immunohistochemistry and slice electrophysiology.

Distinct prefrontal top-down circuits differentially modulate sensorimotor behavior.

Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Modulation by the prefrontal cortex (PFC) is thought to be key for both processes, but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC).

Author Correction: Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex.

Microglia are the brain's resident innate immune cells and also have a role in synaptic plasticity. Microglial processes continuously survey the brain parenchyma, interact with synaptic elements and maintain tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood.

Effects of Developmental Alcohol Exposure on Potentiation and Depression of Visual Cortex Responses.

Background: Neuronal plasticity deficits are thought to underlie abnormal neurodevelopment in fetal alcohol spectrum disorders and in animal models of this condition. Previously, we found that alcohol exposure during a period that is similar to the last months of gestation in humans disrupts ocular dominance plasticity (ODP), as measured in superficial cortical layers. We hypothesize that exposure to alcohol can differentially affect the potentiation and depression of responses that are necessary for activity-dependent sprouting and pruning of neuronal networks.

Fluoxetine modulates breast cancer metastasis to the brain in a murine model.

Background: Despite advances in the treatment of primary breast tumors, the outcome of metastatic breast cancer remains dismal. Brain metastases present a particularly difficult therapeutic target due to the "sanctuary" status of the brain, with resulting inability of most chemotherapeutic agents to effectively eliminate cancer cells in the brain parenchyma. A large number of breast cancer patients receive various neuroactive drugs to combat complications of systemic anti-tumor therapies and to treat concomitant diseases.

Spectral sensitivity of the photointrinsic iris in the red-eared slider turtle (Trachemys scripta elegans).

Our goal in this study was to examine the red-eared slider turtle for a photomechanical response (PMR) and define its spectral sensitivity. Pupils of enucleated eyes constricted to light by ∼11%, which was one-third the response measured in alert behaving turtles at ∼33%. Rates of constriction in enucleated eyes that were measured by time constants (1.

Consensual pupillary light response in the red-eared slider turtle (Trachemys scripta elegans).

Purpose of this study was to determine if the turtle has a consensual pupillary light response (cPLR), and if so, to compare it to its direct pupillary light response (dPLR). One eye was illuminated with different intensities of light over a four log range while keeping the other eye in darkness. In the eye directly illuminated, pupil diameter was reduced by as much as approximately 31%.