Functional organization and natural scene responses across mouse visual cortical areas revealed with encoding manifolds.

A challenge in sensory neuroscience is understanding how populations of neurons operate in concert to represent diverse stimuli. To meet this challenge, we have created "encoding manifolds" that reveal the overall responses of brain areas to diverse stimuli with the resolution of individual neurons and their response dynamics. Here we use encoding manifold to compare the population-level encoding of primary visual cortex (VISp) with five higher visual areas (VISam, VISal, VISpm, VISlm, and VISrl).

Oligodendrocytes and myelin limit neuronal plasticity in visual cortex.

Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity.

Stimulus-specific enhancement in mouse visual cortex requires GABA but not VIP-peptide release from VIP interneurons.

When adult mice are repeatedly exposed to a particular visual stimulus for as little as 1 h per day for several days while their visual cortex (V1) is in the high-gain state produced by locomotion, that specific stimulus elicits much stronger responses in V1 neurons for the following several weeks, even when measured in anesthetized animals. Such stimulus-specific enhancement (SSE) is not seen if locomotion is prevented. The effect of locomotion on cortical responses is mediated by vasoactive intestinal peptide (VIP) positive interneurons, which can release both the peptide and the inhibitory neurotransmitter GABA.

The clustered gamma protocadherin PcdhγC4 isoform regulates cortical interneuron programmed cell death in the mouse cortex.

Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into the cortex where they make connections with locally produced excitatory glutamatergic neurons. Cortical function critically depends on the number of cINs, which is also key to establishing the appropriate inhibitory/excitatory balance. The final number of cINs is determined during a postnatal period of programmed cell death (PCD) when ~40% of the young cINs are eliminated.

Population encoding of stimulus features along the visual hierarchy.

The retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features.

Neurotrophin NT-4/5 Promotes Structural Changes in Neurons of the Developing Visual Cortex.

Current hypotheses on the mechanisms underlying the development and plasticity of the ocular dominance system through competitive interactions between pathways serving the two eyes strongly suggest the involvement of neurotrophins and their high affinity receptors. In the cat, infusion of the tyrosine kinase B ligand (trkB), neurotrophin-4/5 (NT-4/5), abolishes ocular dominance plasticity that follows monocular deprivation (Gillespie et al., 2000), while tyrosine kinase A and C ligands (trkA and trkC) do not have this effect.

Activity-dependent recruitment of inhibition and excitation in the awake mammalian cortex during electrical stimulation.

Electrical stimulation is an effective tool for mapping and altering brain connectivity, with applications ranging from treating pharmacology-resistant neurological disorders to providing sensory feedback for neural prostheses. Paramount to the success of these applications is the ability to manipulate electrical currents to precisely control evoked neural activity patterns. However, little is known about stimulation-evoked responses in inhibitory neurons nor how stimulation-evoked activity patterns depend on ongoing neural activity.

Adolescent oligodendrogenesis and myelination restrict experience-dependent neuronal plasticity in adult visual cortex.

Background: Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this hypothesis in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity.

Population encoding of stimulus features along the visual hierarchy.

The retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features.

The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex.

Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice.

Aberrant cortical spine dynamics after concussive injury are reversed by integrated stress response inhibition.

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability in the world and the strongest environmental risk factor for the development of dementia. Even mild TBI (resulting from concussive injuries) is associated with a greater than twofold increase in the risk of dementia onset. Little is known about the cellular mechanisms responsible for the progression of long-lasting cognitive deficits.

Gamma rhythms and visual information in mouse V1 specifically modulated by somatostatin neurons in reticular thalamus.

Visual perception in natural environments depends on the ability to focus on salient stimuli while ignoring distractions. This kind of selective visual attention is associated with gamma activity in the visual cortex. While the nucleus reticularis thalami (nRT) has been implicated in selective attention, its role in modulating gamma activity in the visual cortex remains unknown.

Clustered gamma-protocadherins regulate cortical interneuron programmed cell death.

Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Here, we show that loss of clustered gamma protocadherins (), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice.

Experience-dependent structural plasticity at pre- and postsynaptic sites of layer 2/3 cells in developing visual cortex.

The developing brain can respond quickly to altered sensory experience by circuit reorganization. During a critical period in early life, neurons in the primary visual cortex rapidly lose responsiveness to an occluded eye and come to respond better to the open eye. While physiological and some of the molecular mechanisms of this process have been characterized, its structural basis, except for the well-known changes in the thalamocortical projection, remains obscure.

Transplanted Cells Are Essential for the Induction But Not the Expression of Cortical Plasticity.

Transplantation of even a small number of embryonic inhibitory neurons from the medial ganglionic eminence (MGE) into postnatal visual cortex makes it lose responsiveness to an eye deprived of vision when the transplanted neurons reach the age of the normal critical period of activity-dependent ocular dominance (OD) plasticity. The transplant might induce OD plasticity in the host circuitry or might instead construct a parallel circuit of its own to suppress cortical responses to the deprived eye. We transplanted MGE neurons expressing either archaerhodopsin or channelrhodopsin into the visual cortex of both male and female mice, closed one eyelid for 4-5 d, and, as expected, observed transplant-induced OD plasticity.

Widespread activation of awake mouse cortex by electrical stimulation.

Electrical stimulation is a highly-effective, temporally-precise technique to evoke neural activity in the brain, and thus is critically important for both research and clinical applications. Here, we set out to understand the time-course and spatial spread of neural activation elicited by electrical stimulation. By imaging the cortex of awake, chronically-implanted, transgenic mice during electrical stimulation, we found that a broad range of stimulation parameters led to widespread neural activation.

Vesicular GABA Transporter Is Necessary for Transplant-Induced Critical Period Plasticity in Mouse Visual Cortex.

The maturation of GABAergic inhibitory circuits is necessary for the onset of the critical period for ocular dominance plasticity (ODP) in the postnatal visual cortex (Hensch, 2005; Espinosa and Stryker, 2012). When it is deficient, the critical period does not start. When inhibitory maturation or signaling is precocious, it induces a precocious critical period.

Flow stimuli reveal ecologically appropriate responses in mouse visual cortex.

Assessments of the mouse visual system based on spatial-frequency analysis imply that its visual capacity is low, with few neurons responding to spatial frequencies greater than 0.5 cycles per degree. However, visually mediated behaviors, such as prey capture, suggest that the mouse visual system is more precise.

Amblyopia: New molecular/pharmacological and environmental approaches.

Emerging technologies are now giving us unprecedented access to manipulate brain circuits, shedding new light on treatments for amblyopia. This research is identifying key circuit elements that control brain plasticity and highlight potential therapeutic targets to promote rewiring in the visual system during and beyond early life. Here, we explore how such recent advancements may guide future pharmacological, genetic, and behavioral approaches to treat amblyopia.

Factors Affecting the Completion of Genitourinary Physical Examinations Prior to Urologic Consultation.

Background: Proper instruction during medical training regarding performing adequate physical examinations prior to urologic consultations greatly improves patient care. We evaluated the frequency of genitourinary (GU) physical examinations performed prior to urologic consultation to determine the influence of factors affecting the completion of these examinations.

Methods: Between January 2013 and December 2014, 1,596 consultations were requested by primary providers and completed by the urology department at a major tertiary care teaching institution.

A real-world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672).

Aim: This is a pre-post observational study from an endocrinology ambulatory care practice which assessed the effectiveness and safety following the addition of a glucagon-like peptide-1 (GLP-1) agonist, weekly exenatide (Bydureon), to basal insulin therapy in patients with type 2 diabetes mellitus (T2DM). Liraglutide plus basal insulin served as a comparison group.

Materials And Methods: A data collection form was utilized to collect study-related information.

Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment.

Interneuron precursors transplanted into visual cortex induce network plasticity during their heterochronic maturation. Such plasticity can have a significant impact on the function of the animal and is normally present only during a brief critical period in early postnatal development. Elucidating the synaptic and physiological properties of interneuron precursors as they mature is key to understanding how long-term circuit changes are induced by transplants.