Saturday, November 23, 2024 11/23/2024

Circuits, Serotonergic Neurons, and the Modulation of Behavior: Characterization of a Specialized Serotonergic Neuron Subtype Responsive to Dopamine and Central to Social Behavior

Award Number: K00NS108515
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/ Abstract Aggression is essential to the survival of organisms as it allows individuals to obtain and defend resources and protect mates or offspring. Yet, aggression can become maladaptive when escalated and unrestrained, sometimes leading to violence in humans. Further, escalated aggression can occur in neuropsychiatric disorders such as intermittent explosive disorder, schizophrenia, and autism. Therefore, advances in understanding the cellular, molecular, and circuit pathways underlying aggression will be significant to human health. Both the serotonergic and dopaminergic neuromodulatory systems are implicated in aggression, yet the specific cell types and circuitry involved are unknown. The proposed research uses cutting-edge genetic and viral tools to understand the role of a specialized dopamine-responsive serotonergic (5-HT) neuron subtype critical to the modulation of aggression, using a mouse model system. This 5-HT neuron subtype is distinguished by the expression of type-II dopamine receptor (Drd2) and the pan serotonergic transcription factor Pet1, and are referred to as Drd2-Pet1 neurons. Largely unknown, is the circuitry involving Drd2-Pet1 neurons and the requirement for the Drd2 receptor in their modulation of behavior. Towards identifying brain regions with inputs onto Drd2-Pet1 neurons, novel viral vectors for intersectional (Cre- and Flp-dependent) trans-synaptic tracing were developed (Aim 1). Additionally, to probe the functional importance of Drd2 in this subset of 5-HT neurons, mice with 5-HT neuron specific deletion of Drd2 were generated and their behavioral phenotype was analyzed in a behavioral screening panel. This work has found that 5-HT neuron expression of Drd2 is critical for the modulation of male aggression and acoustic startle reactivity in females, suggesting a potential sexually dimorphic role (Aim 1). Proposed experiments will further examine the potential sexually dimorphic role of Drd2 expression in 5-HT neurons through the analysis of Drd2-Pet1 neuron modulation of female aggression (Aim 2.1) and characterization of the underlying circuit structure using mouse molecular genetic tools and viral neuronal circuit tracing techniques (Aim 2.2). This PhD dissertation project will inform upon the molecular, cellular, and circuit pathways underlying aggression and startle reactivity while testing novel viral-genetic tools that will be broadly applicable to the study of neuronal subtype connectivity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $96,420 )
2024	2024	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	6/17/2024	NON-COMPETING CONTINUATION	$80,741
2024	2024	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	7/22/2024	NON-COMPETING CONTINUATION	$15,679
														Subtotal = $96,420

Issue Date FY: 2023 ( Subtotal = $80,741 )
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/15/2023	NON-COMPETING CONTINUATION	$80,741
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	8/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $80,741

Issue Date FY: 2022 ( Subtotal = $80,741 )
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/20/2022	NON-COMPETING CONTINUATION	$80,741
														Subtotal = $80,741

Issue Date FY: 2021 ( Subtotal = $80,741 )
2021	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	9/16/2021	EXTENSION WITH OR WITHOUT FUNDS	$80,741
2021	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	9/20/2021	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $80,741

Grand Total All Awards = $338,643

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Circuits, Serotonergic Neurons, and the Modulation of Behavior: Characterization of a Specialized Serotonergic Neuron Subtype Responsive to Dopamine and Central to Social Behavior

Award Number: K00NS108515

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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