Neurobiological processes occurring during puberty that trigger sex differences in learning and memory
New findings suggest optimal teaching tactics, psychiatric treatment,
should adapt to reflect brain differences

Date:
February 10, 2022
Source:
University of California - Irvine
Summary:
New research reveals that sex differences in learning and memory
mechanisms are triggered by biological events occurring during
puberty.

Findings show prepubescent female rodents have much better
hippocampal long-term potentiation (LTP) and spatial learning than
same-age males, but puberty has opposite consequences for synaptic
plasticity in the two sexes.



FULL STORY ==========================================================================
New research from the University of California, Irvine reveals that sex differences in learning and memory mechanisms are triggered by biological events occurring during puberty. Findings show prepubescent female rodents
have much better hippocampal long-term potentiation (LTP) and spatial
learning than same-age males, but puberty has opposite consequences for synaptic plasticity in the two sexes.


==========================================================================
The study, titled "Prepubescent female rodents have enhanced hippocampal
LTP and learning relative to males, reversing in adulthood as inhibition increases" was recently published in Nature Neuroscience.

Since the late 19th century, the general consensus in the scientific
community has been that men outperform women on spatial tasks, while
women excel in learning tasks involving verbal material, while the
general debate has been about why there is a difference.

"The surprising conclusion from our results is that the polarization of
sex differences in hippocampal synapses and related learning reverses in females and males from before to after puberty," said Christine Gall,
PhD, co- corresponding author, and distinguished professor and chair
of anatomy and neurobiology at the UCI School of Medicine. "This occurs
because of distinct developmental changes. Thresholds for plasticity and encoding spatial information increase in females and decease in males."
Puberty is a critical landmark in brain maturation and results in a wide variety of sex differences in behavior, but little is known about how
it affects the substrates for memory encoding. Researchers identified
a female- specific mechanism that increases the LTP threshold and
decreases spatial memory from before to after puberty. Sex differences
were demonstrated for hippocampus-dependent processes and driven by
different underlying mechanisms.

In females only, inhibitory synapses in the CA1 field of the hippocampus exhibit an increase in levels of GABAA receptors containing the ?5
subunit; this increase is associated with greater inhibition of synaptic activity critical for synaptic plasticity and memory. The ?5 receptors
have been linked to anxiety which also undergoes changes at the onset
of the estrous cycle.

Researchers found that pharmacological suppression of ?5-GABAA receptors restored LTP and memory encoding in females to levels observed before
puberty.

"Our team proposes that the emergent female pattern may favor learning
in complex circumstances while the emergent male pattern favors rapid acquisition of simpler material. This idea suggests that optimal teaching strategies need to reflect previously unsuspected brain differences
between the sexes and how these are dramatically adjusted during puberty,"
Gall said. "The vast majority of studies have begun with analyses of young adult male rodents. Females use somewhat different memory mechanisms
than do males and therefore may respond differently to drugs and gene mutations. This new research demonstrates the need for new sexually differentiated approaches for the development of therapeutic treatments
and their applications at different life stages." Further research will
be conducted to determine if the sex-specific LTP threshold changes
identified in hippocampus during the transition to postpubertal life
are evident in other brain areas and influence the encoding of different
types of memories.

Aliza Le, Anatomy & Neurobiology graduate student; Julie Lauterborn, researcher; Yousheng Jia, associate project scientist; Weisheng Wang,
assistant project scientist; Conor Cox, postdoctoral researcher and Gary
Lynch, Psychiatry & Human Behavior professor and co-corresponding author,
all from the UCI School of Medicine, all contributed to the study.

This work was supported by funding from National Institute of Mental
Health training grant T32-MH119049-02; Eunice Kennedy Shriver National Institute of Child Health and Human Development grant HD-089491; National Science Foundation grant BCS-1941216; National Institute on Drug Abuse
grant DA-044118; and Office of Naval Research grant N00014182114; and
National Institutes of Health grant T32 AG00096-34.

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========================================================================== Journal Reference:
1. Aliza A. Le, Julie C. Lauterborn, Yousheng Jia, Weisheng Wang,
Conor D.

Cox, Christine M. Gall, Gary Lynch. Prepubescent female rodents have
enhanced hippocampal LTP and learning relative to males, reversing
in adulthood as inhibition increases. Nature Neuroscience, 2022;
25 (2): 180 DOI: 10.1038/s41593-021-01001-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220210085003.htm

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