New neural circuits discovered that regulate spatial learning and memory
in the brain's hippocampal formation
Understanding of novel functional roles can advance research in
Alzheimer's disease, other learning and memory disorders

Date:
January 10, 2022
Source:
University of California - Irvine
Summary:
A research team has discovered new neural circuits that
regulate spatial learning and memory in the brain's hippocampal
formation. The team identified novel functional roles of new circuit
connections between the venal CA1 region and dorsal CA3 regions of
the hippocampus and demonstrated that genetic inactivation of this
projection impairs object- related spatial learning and memory,
but does not modulate anxiety- related behaviors.



FULL STORY ==========================================================================
A research team led by University of California, Irvine has discovered
new neural circuits that regulate spatial learning and memory in the
brain's hippocampal formation. The team identified novel functional roles
of new circuit connections between the venal CA1 region and dorsal CA3
regions of the hippocampus and demonstrated that genetic inactivation
of this projection impairs object-related spatial learning and memory,
but does not modulate anxiety-related behaviors.


==========================================================================
The study, titled "Non-canonical projections to the hippocampal CA3
regulate spatial learning and memory by modulating the feedforward
hippocampal trisynaptic pathway," was published today in PLOS Biology.

The hippocampus is not a homogenous brain area. The septotemporal axis,
along which the trisynaptic pathway is located, separates the dorsal
region of the hippocampus, which is more involved in learning, memory
and spatial navigation, and the ventral region, which plays a role in
emotional behavior. The trisynaptic's feedforward, unidirectional circuit organization is well documented, but the connectivity across septal to
temporal regions is less well described.

"Our findings extend the knowledge of hippocampal connectivity and its
relation to learning and memory processes across the septotemporal axis
and provide a circuit foundation to explore these novel functional roles,"
said Xiangmin Xu, PhD, Chancellor's Fellow and professor of anatomy and neurobiology, and director for the Center for Neural Circuit Mapping
(CNCM) at the UCI School of Medicine. "The new hippocampal circuit
mechanism is highly relevant to treating learning and memory disorders, including Alzheimer's disease." Building on their earlier work,
Xu and his team used multiple viral tracers, including monosynaptic
rabies retrograde tracing and herpes (H129)-based anterograde tracing to establish new hippocampal CA1 projections to CA3. Robust mapping results
showed that CA1 inputs to CA3 run opposite the trisynaptic pathway and in
a temporal to septal direction. They also found that genetic inactivation
of the CA1 to CA3 projection impaired object-related spatial learning
and memory, but did not modulate anxiety-related behaviors.

"The emergence of viral-genetic mapping techniques enhances our ability
to determine the detailed complexity of brain circuity," Xu said. "Our
study was made possible by the new viral genetic tools developed by our
CNCM investigators at UCI. We are developing these new viral tracers as
brain mapping tools, which we plan to share through our center for use
by the neuroscience community." Other UCI members of the research team
include Xiaoxiao Lin, UCI anatomy and neurobiology graduate student
and first author of the paper; biomedical engineering undergraduate
Michelle Amalraj; Crisylle Blanton and neurobiology undergraduate
researcher Brenda Avila. Other significant contributors to the study
include Douglas A. Nitz, PhD, professor and chair of the Department of Cognitive Science at the University of California, San Diego; and Todd C.

Holmes, PhD, physiology and biophysics professor in the UCI School
of Medicine.

This work was supported by National Institutes of Health BRAIN Initiative grants NS078434 and MH120020; and an NIH R35 grant GM127102.

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========================================================================== Journal Reference:
1. Xiaoxiao Lin, Michelle Amalraj, Crisylle Blanton, Brenda Avila,
Todd C.

Holmes, Douglas A. Nitz, Xiangmin Xu. Noncanonical projections
to the hippocampal CA3 regulate spatial learning and memory by
modulating the feedforward hippocampal trisynaptic pathway. PLOS
Biology, 2021; 19 (12): e3001127 DOI: 10.1371/journal.pbio.3001127 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220110114159.htm
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