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The Development of Facial Motor Neuron Subtypes in Health and in Congenital Facial Weakness

Award Number: K00NS120596
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/25/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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The Development of Facial Motor Neuron Subtypes in Health and in Congenital Facial Weakness - PROJECT SUMMARY Aberrant changes in mature neural connections and their function can be induced by infection and inflammation within the brain. The intracellular protozoan parasite, Toxoplasma gondii, is one pathogen that infects the brain, evokes a prolonged inflammatory response and can cause seizures. Persistent infection by this parasite is also associated with behavioral alterations and is a considerable risk factor for developing psychiatric illness, includ- ing schizophrenia. Over 30% of Americans are presently living with an incurable long-term infection of Toxo- plasma gondii, yet, despite its prevalence and implications for serious neurological disorders, we lack sufficient understanding of the effect of life-long parasitic infection on the brain – a major organ of the human body in which the parasite invades cells. This study seeks to elucidate the underlying mechanisms of brain circuitry dysregu- lation in long-term infection in response to this unmet need. Our recent studies have revealed that Toxoplasma gondii brain infection causes changes in inhibitory circuitry (specifically the loss of inhibitory synapses) along with changes in inhibitory neurotransmission, leading to the onset of seizures. Moreover, preliminary studies demonstrating increased expression of classical complement cascade components, elevated microglial activa- tion, and substantial microglial ensheathment of neurons and inhibitory nerve terminals, propose dynamic inter- active roles for the innate immune system and resident-macrophages of the brain in altering functionally mature neural circuits during parasitic infection. In this proposal, we test the hypotheses that molecular components of the innate complement pathway mediate inhibitory synapse loss and seizures, and that microglia remove and phagocytose these synapses following chronic Toxoplasma gondii infection. By capitalizing on multi-scale imag- ing modalities, the aims in this proposal will deliver novel ultrastructural and real-time insight into the impact of chronic parasitic infection on mature neural circuits and will offer a novel mechanism as to how persistent Toxo- plasma gondii infection may contribute to both seizures and psychiatric illness. This study is directly aligned with the NIH's Blueprint Program's mission to expand our understanding of the neuroimmune dynamic interactions that give way to neurological disorders.


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: 2026 ( Subtotal = $100,588 )
2026	2026	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/17/2025	NON-COMPETING CONTINUATION	$100,588
														Subtotal = $100,588

Issue Date FY: 2025 ( Subtotal = $96,281 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/10/2024	NON-COMPETING CONTINUATION	$96,281
														Subtotal = $96,281

Issue Date FY: 2024 ( Subtotal = $91,975 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/19/2023	NON-COMPETING CONTINUATION	$86,065
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/9/2024	NON-COMPETING CONTINUATION	$5,910
														Subtotal = $91,975

Issue Date FY: 2023 ( Subtotal = $86,065 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/14/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/8/2023	EXTENSION WITH OR WITHOUT FUNDS	$86,065
														Subtotal = $86,065

Grand Total All Awards = $374,909

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The Development of Facial Motor Neuron Subtypes in Health and in Congenital Facial Weakness

Award Number: K00NS120596

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/25/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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