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High throughput molecular screen for environmental epigenetic modifiers in brain development and ASD

Award Number: K00ES032608
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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High throughput molecular screen for environmental epigenetic modifiers in brain development and ASD - Oxytocin is a peptide and hormone known to be involved in myriad social behaviors. Dysfunction of the oxytocinergic signaling has also been implicated in the etiology of social deficits and neuropsychiatric disease. The mechanisms of oxytocin signaling in the brain, however, are incompletely understood. In this proposal, we dissect oxytocinergic signaling in the hippocampal subregion CA2, which is known to be a locus of oxytocin signaling and has, itself, been implicated in social behavior. Aim 1 of the proposal describes our lab's recent work elucidating the mechanism of oxytocin-driven excitation in hippocampal neurons. Activation of the oxytocin receptor (OXTR) depolarizes CA2 pyramidal cells by activation of a Gq-coupled signaling pathway that ultimately inhibits a potassium current known the M-current, or IM. Described most thoroughly in CA2 pyramidal cells, this mechanism appears to generalize to interneurons in CA1 and CA2. Joint regulation of excitatory and inhibitory neurons in CA2 shapes the propagation of activity from CA2 to its primary downstream target CA1. In addition to excitation, OXTR stimulation can cause hyperpolarization of hippocampal neurons. Experiments described in Aim 2 deconstruct the two opposing mechanisms downstream of the OXTR, with particular emphasis on how they produce the complex dynamics recorded in vitro. Moreover, we build upon the observation that there at least two subpopulations of CA2 pyramidal cells, only one of which expresses the OXTR. We propose experiments to compare the inputs, outputs and intrinsic properties of these two subpopulations. Aim 2 concludes with behavioral experiments driven by the hypothesis that oxytocin is necessary for CA2-mediated social behavior. Aim 3 describes work to be completed in the postdoctoral training period, using ethologically relevant behaviors to drive in vitro mechanistic studies. In vivo recordings will bridge biophysical and behavioral observations. This methodology will be applied to the investigation of social behaviors, with particular emphasis on how neural dynamics are modulated.


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 = -$14,267 )
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Environmental Health	000	6	8/28/2024	NON-COMPETING CONTINUATION	-$14,267
														Subtotal = -$14,267

Issue Date FY: 2023 ( Subtotal = $84,750 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Environmental Health	000	6	2/24/2023	NON-COMPETING CONTINUATION	$84,750
														Subtotal = $84,750

Issue Date FY: 2022 ( Subtotal = $84,750 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Environmental Health	000	5	3/2/2022	NON-COMPETING CONTINUATION	$84,750
														Subtotal = $84,750

Issue Date FY: 2021 ( Subtotal = $84,750 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Environmental Health	000	4	3/1/2021	NON-COMPETING CONTINUATION	$84,750
														Subtotal = $84,750

Issue Date FY: 2020 ( Subtotal = $84,750 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Environmental Health	001	3	6/3/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$11,094
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Environmental Health	000	3	5/7/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$73,656
														Subtotal = $84,750

Grand Total All Awards = $324,733

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High throughput molecular screen for environmental epigenetic modifiers in brain development and ASD

Award Number: K00ES032608

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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