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Behavioral effects of igsf9b in the prefrontal cortex

Award Number: R21MH121836
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Behavioral effects of igsf9b in the prefrontal cortex - Behavioral Effect of IgSF9b in the Prefrontal Cortex Abstract IgSF9b was recently identified as a high-risk gene strongly associated with negative symptoms of schizophrenia (SZ) and major depressive disorders (MDD). IgSF9b gene codes for adhesion protein IgSF9b, which is specifically expressed in the brain, especially in the forebrain region of the neocortex. In vitro studies indicate IgSF9b is primarily expressed in GABAergic interneurons and subset of pyramidal neurons, with coupling to neuroligin 2 to promote inhibitory signaling. However, whether and how IgSF9b deficiency affects cognitive and social behaviors, especially those related to social withdrawal and anhedonia, remains untested. We endeavored to explore the functional roles of protein IgSF9b in the medial prefrontal cortex (mPFC) in the regulation of motivational and social behaviors as this brain region is highly associated with executive function, cognition, and social behavior control, as well as deficits related to depression and SZ. Our studies aim to elucidate the fundamental physiological role of protein IgSF9b, at a cellular, circuit, and behavioral level. In our pilot study, we performed successful knockdown (KD) of protein IgSF9b in the young adult mouse mPFC, and interestingly, we found that IgSF9b KD significantly impairs both social preference and social memory. We hypothesize that selective KD of IgSF9b impairs behaviors associated with social withdrawal and anhedonia by reducing inhibition and affecting neurons projecting to subcortical areas related to social behavior such as nucleus accumbens (NAc). We will first evaluate the effects of IgSF9b KD in the mPFC on motivational and social withdrawal behaviors and then determine whether IgSF9b KD in the mPFC selectively affects the mPFC-NAc pathway to regulate social behaviors. IgSF9b is mainly expressed in the forebrain of the neocortex and is proposed to be highly associated with negative symptoms. Therefore, examining the effects of IgSF9b on mPFC-associated behaviors has the potential to elucidate unidentified mechanisms of behavioral deficits seen in neuropsychiatric diseases such as SZ.


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: 2025 ( Subtotal = -$69 )
2025	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	12/5/2024	NEW	-$69
														Subtotal = -$69

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	8/8/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $425,236 )
2020	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	7/31/2020	NEW	$425,236
														Subtotal = $425,236

Grand Total All Awards = $425,167

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Behavioral effects of igsf9b in the prefrontal cortex

Award Number: R21MH121836

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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