Gavin R Rumbaugh

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Learning and Memory
• Developmental Cognitive Neuroscience
• ADHD
• Autism Spectrum Disorder
• Neuroplasticity and Neural Repair
• Neuroimaging

Active NIH awards

• Intersection of causal neurodevelopmental disorder risk genes, cortical circuit function, and cognitive processing required for behavioral adaptions

  5R01MH096847-14

  NIMH · FY 2025 · $891K

  PROJECT SUMMARY Neurodevelopmental disorders (NDDs), like most neuropsychiatric disorders, are defined in general terms through cognitive impairment and behavioral alterations. Advances in genome sequencing from large patient populations has led to the identification of genes that cause complex NDDs. As a result, a major area of basic research related to NDDs is to understand how these high-impact genetic risk factors disrupt molecular and cellular mechanisms in brain cells and how these cellular alterations translate to changes in circuitry and behavior. This ongoing R01 has historically focused on the neurobiological impact of a consensus NDD risk gene, Syngap1, on the assembly and function of cortical synaptic connectivity in mice. In the current budget period, we have made progress toward understanding the extent of touch-mediated behavioral deficits and dysfunction within cortical circuitry that processes touch in the Syngap1 mouse model. The upcoming budget period seeks to understand the cause-and-effect relationships between altered assembly, function, and plasticity of cortical circuits and touch-associated behavioral maladaptations in this model. Based on mounting published and unpublished preliminary data, we will test the overarching hypothesis that Syngap1 regulates cognitive function and behavior by sculpting cortical circuits that promote tactile perception. This hypothesis is relevant to NDD etiology because altered sensory processing is a ubiquitous manifestation of NDDs, including ASD, SCZ, and ADHD. An idea gaining momentum in the field is that alterations to cognitive function and behavior are caused, at least in part, through impaired sensory processing within cortical circuits. This research topic is relevant to mental health disorders because cognitive function is a major domain of brain function and perception is a construct that defines it. However, the circuits that support perception, how they directly impact behaviors relevant to mental health disorders, and how major genetic risk factors regulate them, remains poorly understood. Aim 1 will determine how Syngap1 expression within tactile processing cortical neurons contributes to tactile learning and behavioral phenotypes in Syngap1 mice. Aim 2 studies will determine how Syngap1 regulates mesoscale cortical plasticity during tactile learning. Aim 3 is designed to provide insight into how Syngap1 expression in forebrain excitatory neurons contributes to modulation of hindbrain arousal centers that support reinforcement learning. Overall Impact: The proposed research has the potential to define cortical circuits that causally link impaired sensory processing directly to NDD-associated cognitive and behavioral impairments. Such studies are expected to inform the growing idea in the field that impaired cortical sensory processing directly leads to behavioral maladaptations common to NDDs.

• Neurodevelopmental Disorder Risk Gene Regulation of Intrinsic Membrane Excitability: A Rheostat that Tunes Dendritic Morphogenesis to Regulate Circuit Assembly During Development

  5R01MH131788-04

  NIMH · FY 2025 · $678K

  Project Summary The goal of this project is to understand how gene expression during development shapes the delicate and massively parallel cell biological processes that promote wiring of functional networks within the cerebral cortex. This is an important area of basic research because neural dynamics within cortical networks are the direct correlates of thought and behavior. These cognitive processes emerge as neural circuits form through expression of genes over the course of development. Moreover, cognitive impairment, which defines neurodevelopmental disorders (NDDs), is thought to arise, at least in part, from impaired neural circuit connectivity within the developing cortex. A revelation over the past decade is that NDDs can be caused by de novo genetic loss-of-function SNVs within a single gene. Thus, in-depth study of natural functions of these genes can reveal the neurobiological principles underlying the typically developing cortex and as well as principles that contribute to abnormal cortical development associated with NDDs. In this project, we will explore the hypothesis that expression of NDD-associated genes in the typically developing cortex promotes the assembly of cortical circuits through cell-autonomous regulation of intrinsic membrane excitability. This hypothesis is significant because it is known that neural activity shapes the assembly of developing cortical circuits. However, it remains unknown how genes function at the cellular level to promote activity-dependent in vivo development of cortical circuit motifs known to promote cognitive function and behavioral adaptations. Aim 1 will explore the causal relationships between genetic control of intrinsic membrane excitability (IME), activity- dependent dendritic morphogenesis, and developmental assembly of cortical circuits. Aim 2 will explore causal links between genetic control of IME, neuronal ensemble structure/function, and behavioral adaptations. We will do this by regulating genetic control of IME in developing cortical neurons and then observing the effect of this on cortical ensembles and behavioral adaptions. This research design is important because the brain functions across multiple temporal and spatial scales – indeed, this project attempts to link gene function across the major levels of brain function – gene>neuron>synapse>circuit>ensemble>behavior. The overall impact of this proposed research is that it has the potential to reveal how gene expression shapes the activity- dependent assembly of neural circuits that promote cognitive functions required for behavioral adaptations. Because we focus on natural functions of an NDD gene, these basic insights are also directly relatable to the etiology of cortical wiring impairments associated with childhood brain disorders.