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Principal Investigator: Alessandra Angelucci
Organization: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
Fiscal Year: 2024
Award: $424,941
Funding agency: National Eye Institute
PROJECT SUMMARY
In the mammalian neocortex, inhibitory neurons (INs) profoundly influence cortical computations and
dynamics, and their various functions are thought to be mediated by different IN types. While a large diversity
of INs exists, molecular markers in mouse cortex identify three major non-overlapping classes: parvalbumin-
(PV), somatostatin- (SOM), and vasoactive intestinal peptide- (VIP) INs. Studies in mouse lines expressing
Cre-recombinase in each of these IN classes are rapidly revealing distinct patterns of connectivity, response
properties and in vivo function for each class. However, it remains unknown whether insights gained from
mouse cortex apply to cortical INs in primates and humans. IN dysfunction in humans has been implicated in
several disorders, such as epilepsy, schizophrenia, anxiety and autism, therefore it is important to understand
normal cortical IN connectivity and function in primates. The lack of viral tools to selectively access IN
subtypes, and the difficulty of performing genetic manipulations in primates have been major impediments to
studying INs in this animal model. Our goal is to leverage recent advances in the development of viral tools to
express transgenes in specific INs subtypes to investigate the connectivity, response properties, and
computational function of two major classes of INs, PV and SOM, in the superficial layers of the primate
primary visual cortex (V1). Using IN-type specific expression of Cre-recombinase combined with rabies-virus
monosynaptic circuit tracing, we will map local and brain-wide inputs to specific V1 IN classes (Aim1). Using
two-photon imaging of IN-type specific targeted calcium indicators, or optogenetic identification of
channelrhodopsin-tagged IN types, we will characterize the visual response properties of distinct V1 IN classes
(Aim2). Finally, we will use optogenetic inactivation of distinct IN-types expressing inhibitory opsins, to
understand the relative roles of IN classes in V1 computations (Aim3). We will test specific hypotheses derived
from available data in mouse, the specific geometry of PV and SOM cells in primate cortex, published
computational models of feature tuning and surround suppression in visual cortex, and our preliminary
results. Impact. The proposed studies will provide the first account of the connectivity, visual properties and
computational function of PV and SOM INs in primate cortex, paving the way for studies of IN function in this
order. They will also reveal conserved principles of IN function across species, as well as fundamental inter-
species differences, stressing the importance of studying cortical function in species that are evolutionarily
closer to humans.
Terms: <2-photon><ASD><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Anxiety><Apoplexy><Area><Autism><Autistic Disorder><Autopsy><Axon><Basket Cell><Behavioral><Biologic Models><Biological Models><Brain><Brain Nervous System><Brain Vascular Accident><CRE Recombinase><Calcium><Callithrix><Cell Body><Cell Nucleus><Cells><Cerebral Stroke><Cerebral cortex><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Chemicals><Computer Models><Computerized Models><Contrast Sensitivity><Cyclic Somatostatin><D Cells><Data><Defect><Delta Cell><Dendrites><Development><Disease><Disorder><Dysfunction><Early Infantile Autism><Electrodes><Electrophysiology><Electrophysiology (science)><Encephalon><Enterobacteria phage P1 Cre recombinase><Epilepsy><Epileptic Seizures><Epileptics><Equilibrium><Explosion><Feedback><Foundations><Functional disorder><Gene Expression><Geometry><Glutamates><Goals><Growth Hormone Inhibiting Factors><Growth Hormone-Inhibiting Hormone><Hapale><Human><Image><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Infantile Autism><Kanner's Syndrome><Knowledge><L-Glutamate><Lateral><Literature><Location><Maps><Marmosets><Measures><Mediating><Mental disorders><Mental health disorders><Mice><Mice Mammals><Model System><Modern Man><Morphology><Murine><Mus><Myoepithelial cell><Neocortex><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurocyte><Neurologic><Neurologic Disorders><Neurological><Neurological Disorders><Neuronal Dysfunction><Neurons><Neurophysiology / Electrophysiology><Nucleus><Opsin><PHM27><Parvalbumins><Pattern><Physiologic><Physiological><Physiopathology><Population><Primary visual cortex><Primates><Primates Mammals><Property><Psychiatric Disease><Psychiatric Disorder><Publishing><Rabies lyssavirus><Rabies mapping><Rabies trans synaptic tracing><Rabies virus><Rabies virus mediated mapping><Recurrence><Recurrent><Rod-Opsin><Rodent><Rodentia><Rodents Mammals><Role><SRIH><SRIH-14><Schizophrenia><Schizophrenic Disorders><Seizure Disorder><Sensory><Short-Tusked Marmoset><Sight><Somatostatin><Somatostatin Cells><Somatostatin Secreting Cell><Somatostatin-14><Somatotropin Release Inhibiting Factors><Somatotropin Release-Inhibiting Hormone><Source><Stimulus><Stress><Striate Cortex><Striate area><Stroke><Technology><Testing><Transgenes><Transmission><V1 neuron><Vasoactive Intestinal Peptide><Vasoactive Intestinal Polypeptide><Vasointestinal Peptide><Viral><Vision><Visual><Visual Contrast Sensitivity><Visual Cortex><Work><abnormal brain function><area striata><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><bacteriophage P1 recombinase Cre><balance><balance function><brain attack><brain dysfunction><brain impairment><calcium indicator><cell type><cerebral vascular accident><cerebrovascular accident><computational modeling><computational models><computer based models><computerized modeling><dementia praecox><developmental><dysfunctional brain><electrophysiological><epilepsia><epileptogenic><gene manipulation><genetic manipulation><genetically manipulate><genetically perturb><glutamatergic><growth hormone release inhibiting factor><homotypical cortex><imaging><in vivo><inhibitory neuron><insight><isocortex><mental illness><model of animal><molecular biomarker><molecular marker><necropsy><neopallium><neural cell body><neural circuit><neural circuitry><neural dysfunction><neurocircuitry><neurological disease><neuronal><neuronal cell body><optogenetics><pathophysiology><postmortem><psychiatric illness><psychological disorder><rabies based mapping><rabies based retrograde mapping><rabies circuit tracing><rabies mediated retrograde monosynaptic tracing><rabies retrograde tracing><rabies tracer><rabies tracing><rabies viral tracing><rabies virus mediated circuit mapping><rabies virus monosynaptic circuit tracing><rabies virus monosynaptic tracing><rabies virus retrograde tracing><rabies virus tracing><receptive field><response><schizophrenic><selective expression><selectively expressed><sensory cortex><social role><soma><stroked><strokes><synaptic circuit><synaptic circuitry><tool><tracing with rabies><transgene><transmission process><two-photon><visual cortical><visual function><visual process><visual processing><visual stimulus>