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Principal Investigator: MARNIE E HALPERN
Organization: DARTMOUTH COLLEGE
Fiscal Year: 2024
Award: $498,270
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
ABSTRACT/PROJECT SUMMARY
The habenulo-interpeduncular pathway, a forebrain to midbrain conduction system in the
vertebrate brain, has been implicated in many essential processes, from sleep to fear/anxiety,
pain, learning, motivation, feeding, reproduction, and reward, and in pathological states such
as mood disorders and addiction. Despite its importance and diverse roles, little is known
about the complete repertoire of neuronal subpopulations and precise connectivity between
the bilaterally paired dorsal habenular nuclei (dHb) of the dorsal diencephalon and their major
target, the unpaired interpeduncular nucleus (IPN) of the ventral midbrain. A renewed interest
in this pathway came from its association with nicotine dependence and withdrawal and from
the discovery that, in zebrafish and other vertebrates, the dHb develop with prominent left-right differences in their size, organization, molecular properties and connections to the IPN.
In previous work, we described an asymmetric olfactory projection to a subset of neurons in
the right dHb that helps mediate the response to aversive cues and determined that altering
directional asymmetry of the dHb induces behavioral and physiological changes indicative of
enhanced fear/anxiety. Using state-of-the-art genetic, transgenic, imaging, and behavioral
approaches, we now aim to identify all of the neuronal populations of the Hb-IPN pathway
and further define which groups of neurons are involved in the response to negative cues.
We have also extended our studies to characterize the pre-synaptic input and post-synaptic
targets of this conduction system to gain a more complete understanding of the underlying
neural circuits and their connectivity. The proposed research will shed light on a poorly
understood yet highly conserved neural pathway and also address how differential
processing of information by neurons on the left and right sides of the brain leads to
appropriate behavioral responses.
Terms: <ASD><Address><Affective Disorders><Amphibia><Amphibians><Anxiety><Assay><Atlases><Attention><Autism><Autistic Disorder><Axon><Axon Terminals><Behavior><Behavioral><Behavioral Assay><Bilateral><Bioassay><Biological Assay><Body Tissues><Brachydanio rerio><Brain><Brain Nervous System><Brain region><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Calcium><Calcium Ion Signaling><Calcium Signaling><Cas nuclease technology><Cell Body><Cell Communication and Signaling><Cell Isolation><Cell Nucleus><Cell Segregation><Cell Separation><Cell Separation Technology><Cell Signaling><Cells><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Coupled><Cues><Danio rerio><Data><Data Set><Decision Making><Development><Dorsal><Dysfunction><Dyslexia><Early Infantile Autism><Encephalon><Fear><Fishes><Fore-Brain><Forebrain><Freezing><Fright><Functional disorder><Funding><Future><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Genes><Genetic><Genomics><Goals><Habenular Nucleus><Human><Image><Infantile Autism><Intracellular Communication and Signaling><Kanner's Syndrome><Label><Learning><Left><Locomotion><Mammalia><Mammals><Maps><Mediating><Mental Depression><Mesencephalon><Mid-brain><Midbrain><Midbrain structure><Modeling><Modern Man><Molecular><Monitor><Mood Disorders><Motivation><Nerve Cells><Nerve Conduction><Nerve Transmitter Substances><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neural Conduction><Neural Pathways><Neurocyte><Neurologic><Neurologic Disorders><Neurological><Neurological Disorders><Neurons><Neuropeptides><Neurophysiology - biologic function><Neurosciences Research><Neurotoxins><Neurotransmitters><Nicotine Dependence><Nicotine Withdrawal><Nucleus><Pain><Painful><Pathologic><Pathway interactions><Physiologic><Physiological><Physiopathology><Population><Presynaptic Nerve Endings><Presynaptic Terminals><Process><Progress Reports><Property><Prosencephalon><Reagent><Reproduction><Reptiles><Reptilia><Research><Research Resources><Resources><Rewards><Role><Sample Size><Schizophrenia><Schizophrenic Disorders><Side><Signal Transduction><Signal Transduction Systems><Signaling><Sleep><Stimulus><Synaptic Boutons><Synaptic Terminals><System><Time><Tissues><Transcript Expression Analyses><Transcript Expression Analysis><Transgenic Organisms><Vertebrate Animals><Vertebrates><Withdrawal Symptom><Word Blindness><Work><Zebra Danio><Zebra Fish><Zebrafish><addiction><addictive disorder><analyze gene expression><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><behavior outcome><behavior response><behavioral outcome><behavioral response><biological signal transduction><calcium indicator><cell sorting><cell type><cholinergic><circadian><confocal imaging><dementia praecox><depression><developmental><diencephalon><experiment><experimental research><experimental study><experiments><feeding><gene expression analysis><gene expression assay><genome editing><genomic editing><imaging><in vivo><information processing><innovate><innovation><innovative><interest><interpeduncular nucleus><multi-photon><neural circuit><neural circuitry><neural function><neural imaging><neuro-imaging><neurocircuitry><neuroimaging><neurological disease><neurological imaging><neuronal><neurotoxicant><nicotine addiction><nicotine dependent><optogenetics><pathophysiology><pathway><postsynaptic><presynaptic><real-time images><realtime image><response><schizophrenic><social role><synaptic circuit><synaptic circuitry><tool><transcriptional profiling><transgenic><vertebrata>