A central goal of neuroscience research is to understand how experiences modify brain circuits to guide future adaptive behavior. In response to environmental stimuli, neural circuit activity engages gene regulatory mechanisms within each cell. This activity-dependent gene expression is governed, in part, by epigenetic processes that can produce persistent changes in both neural circuits and the epigenome itself. The complex interplay between circuit activity and neuronal gene regulation is vital to learning and memory, and, when disrupted, is linked to debilitating psychiatric conditions, such as substance use disorder. To develop clinical treatments, it is paramount to advance our understanding of how neural circuits and the epigenome cooperate to produce behavioral adaptation. Here, we discuss how new genetic tools, used to manipulate neural circuits and chromatin, have enabled the discovery of epigenetic processes that bring about long-lasting changes in behavior relevant to mental 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. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorder...

Each year, JNeurosci publishes a group of review articles based on topics presented in symposia and mini-symposia at the annual meeting of the Society for Neuroscience. These reviews are usually published in a special issue the week before the meeting. Sadly, the 2020 annual meeting was canceled

Spinal interneurons are important facilitators and modulators of motor, sensory, and autonomic functions in the intact CNS. This heterogeneous population of neurons is now widely appreciated to be a key component of plasticity and recovery. This review highlights our current understanding of spinal interneuron heterogeneity, their contribution to control and modulation of motor and sensory functions, and how this role might change after traumatic spinal cord injury. We also offer a perspective for how treatments can optimize the contribution of interneurons to functional improvement.

Animals engage in routine behavior in order to efficiently navigate their environments. This routine behavior may be influenced by the state of the environment, such as the location and size of rewards. The neural circuits tracking environmental information and how that information impacts decisions to deviate from routines remains unexplored. To investigate the representation of environmental information during routine foraging, we recorded the activity of single neurons in posterior cingulate cortex (PCC) in two male monkeys searching through an array of targets in which the location of rewards was unknown. Outside the laboratory, people and animals solve such traveling salesman problems by following routine traplines that connect nearest-neighbor locations. In our task, monkeys also deployed traplining routines, but as the environment became better known, they deviate from them despite the reduction in foraging efficiency. While foraging, PCC neurons tracked environmental information but not reward and ...

A fundamental, evolutionarily conserved biological mechanism required for long-term memory formation is rapid induction of gene transcription upon learning in relevant brain areas. For episodic types of memories, two regions undergoing this transcription are the dorsal hippocampus (dHC) and prelimbic (PL) cortex. Whether and to what extent these regions regulate similar or distinct transcriptomic profiles upon learning remains to be understood. Here, we used RNA sequencing in the dHC and PL cortex of male rats to profile their transcriptomes in untrained conditions (baseline) and at 1 hour and 6 days after inhibitory avoidance learning. We found that, out of 33,713 transcripts, over 14,000 were significantly expressed at baseline in both regions and approximately 3,000 were selectively enriched in each region. Gene Ontology biological pathway analyses indicated that commonly expressed pathways included synapse organization, regulation of membrane potential, and vesicle localization. The enriched pathways i...

Early life is a sensitive period in which enhanced neural plasticity allows the developing brain to adapt to its environment. This plasticity can also be a risk factor in which maladaptive development can lead to long-lasting behavioral deficits. Here, we test how early-life exposure to the selective-serotonin-reuptake-inhibitor, fluoxetine, affects motivation and dopaminergic signaling in adulthood. We show for the first time that mice exposed to fluoxetine in the early postnatal period exhibit a reduction in effort-related motivation. These mice also show blunted responses to amphetamine and reduced dopaminergic activation in a sucrose reward task. Interestingly, we find that the reduction in motivation can be rescued in the adult by administering bupropion, a dopamine-norepinephrine reuptake inhibitor used as an antidepressant and a smoke cessation aid, but not by fluoxetine. Taken together, our studies highlight the effects of early postnatal exposure of fluoxetine on motivation and demonstrate the in...

Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulfate proteoglycans (CSPGs), which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase ABC (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates brain-derived neurotrophic factor (BDNF)-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase σ (PTPσ, PTPRS), receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTPσ deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTPσ-de...

High digital connectivity and a focus on reproducibility are contributing to an open science revolution in neuroscience. Repositories and platforms have emerged across the whole spectrum of subdisciplines, paving the way for a paradigm shift in the way we share, analyze, and reuse vast amounts of data collected across many laboratories. Here, we describe how open access web-based tools are changing the landscape and culture of neuroscience, highlighting six free resources that span subdisciplines from behavior to whole-brain mapping, circuits, neurons, and gene variants.

Source memory improves substantially during childhood. This improvement is thought to be closely related to hippocampal maturation. As previous studies have mainly used cross-sectional designs to assess relations between source memory and hippocampal function, it remains unknown whether changes in the brain precede improvements in memory or vice versa. To address this gap, the current study used an accelerated longitudinal design ( n = 200, 100 males) to follow 4- and 6-year-old human children for 3 years. We traced developmental changes in source memory and intrinsic hippocampal functional connectivity and assessed differences between the 4- and 6-year-old cohorts in the predictive relations between source memory changes and intrinsic hippocampal functional connectivity in the absence of a demanding task. Consistent with previous studies, there were age-related increases in source memory and intrinsic functional connectivity between the hippocampus and cortical regions known to be involved during memory e...