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Principal Investigator: Andrew George Gordus
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $43,370
Funding agency: National Institute of General Medical Sciences
The Influence of Neuronal States on Perception and Behavior
Unlike reflexes, most of our behaviors are governed by internal states such as satiety or arousal that influence how we
respond to our environment. The ability to regulate our internal state in response to experience is immediately evident
in mental pathologies where this process is broken. In maladaptive disorders such as Attention Hyperactivity Deficit
Disorder (ADHD) or Post-Traumatic Stress Disorder (PTSD), the brain’s ability to properly coordinate salient sensory
inputs with appropriate behavioral responses is fundamentally flawed, and in extreme psychiatric disorders such as
schizophrenia, sensory information is nearly shut-out entirely, as nearly all behaviors are driven by internal
representations of the world, i.e. hallucinations and delusions. Functional understandings of how these disorders arise
are very limited, in part because of the complexity of the underlying processes that produce these behaviors. However,
researching internal states in non-humans is challenging for two reasons. 1. These states are often encoded by
neuromodulators, but are behaviorally defined based on the probabilities of observed behaviors; the organisms often do
not leave a record of their intent. To simplify analysis, these assays often investigate binary states such as satiety vs.
hunger, arousal vs. not aroused, even though natural behaviors are not necessarily bimodal. 2. How neuromodulators
alter specific synaptic relationships in a circuit is daunting in unannotated, complex circuits.
However, both of these challenges can be addressed by using the right model system. Animals that build structures in
defined phases, such as orb-weaving spiders, leave a physical record of their behavioral intent, thus simplifying the
definition of behavioral states. These paradigms are also more ethologically relevant, as the animals are allowed to
perform complex behaviors without the need for learning an artificial binary tasks. Likewise, small animals like C. elegans
have defined and annotated synaptic topologies that can be investigated under different neuromodulatory contexts,
providing us with an unparalleled ability to understand neuromodulatory rewiring with single neuron resolution. More
specifically, how neuron computations like synergistic integration are altered can be addressed in explicitly defined
neurons and synapses. My long-term goal is to understand how internal states organize behavior, and more explicitly,
how the neuromodulators that define these states alter the function of neuronal circuits.
We aim to make two key advancements in the field. 1) We will build a neuromodulatory map of how these pathways
coordinate multiple behaviors beyond a binary paradigm. 2) We will quantify how internal states modulate synergistic
coupling between neurons.
Terms: <Address><Animals><Architecture><Arousal><Assay><Attention><Behavior><Behavioral><Bioassay><Biologic Models><Biological Assay><Biological Models><Brain><Brain Nervous System><C elegans><C. elegans><C.elegans><Caenorhabditis elegans><Complex><Coupling><Delusions><Disease><Disorder><Encephalon><Engineering / Architecture><Environment><Goals><Hallucinations><Hunger><Hyperactivity><Invertebrata><Invertebrates><Learning><Maps><Mental disorders><Mental health disorders><Modality><Model System><Motivation><Nematoda><Nematodes><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neuromodulator><Neurons><Organism><PTSD><Pathology processes><Pathway interactions><Perception><Phase><Post-Traumatic Neuroses><Post-Traumatic Stress Disorders><Posttraumatic Neuroses><Probability><Process><Psyche structure><Psychiatric Disease><Psychiatric Disorder><Reflex><Reflex action><Resolution><Satiation><Schizophrenia><Schizophrenic Disorders><Sensory><Spiders><Structure><Synapses><Synaptic><behavior response><behavioral response><dementia praecox><experience><living system><mental><mental illness><neural control><neural regulation><neuromodulation><neuromodulatory><neuronal><neuronal circuit><neuronal circuitry><neuroregulation><pathway><post-trauma stress disorder><posttrauma stress disorder><psychiatric illness><psychological disorder><resolutions><response><roundworm><satiety><schizophrenic><sensory input><synapse><traumatic neurosis>