New research has highlighted a female-specific memory mechanisms leading to differences in learning between males and females, which are triggered by biological events occurring during puberty. The research, by scientists from the University of California, Irvine(UCI), further found that pharmacological intervention could restore these key memory mechanisms – in females – to levels observed before puberty.

New research has highlighted a female-specific memory mechanism leading to differences in learning between males and females, which are triggered by biological events occurring during puberty. The research, by scientists from the University of California, Irvine (UCI), further found that pharmacological intervention could restore these key memory mechanisms – in females – to levels observed before puberty.

In the study, female rodents were noticed to have “enhanced hippocampal long-term potentiation (LTP) and spatial learning relative to males,” that has been beneficial to learning tasks involving verbal material. However, hippocampal LTP reverses in adulthood due to inhibition of synaptic activity.

“The polarisation of sex differences in hippocampal synapses and related learning reverses in females and males from before to after puberty occurs because of distinct developmental changes. Thresholds for plasticity and encoding spatial information increase in females and decease in males.” said Dr. Christine Gall, distinguished professor and chair of anatomy and neurobiology at the UCI School of Medicine.

The scientists identified sex differences in hippocampus-dependent processes, driven by different underlying mechanisms – more specifically, they identified a mechanism specific to females that increases their LTP threshold and decreases spatial memory from before to after puberty.

In females only, inhibitory synapses in the hippocampus exhibit an increase in the levels of neurotransmitter (GABAA) receptors containing what is known as the α5 subunit; this increase is associated with greater inhibition of synaptic activity critical for synaptic plasticity and memory. The α5 receptors have been linked to anxiety which also undergoes changes at the onset of the estrous cycle (in puberty).

The scientists later found that pharmacological suppression of α5-GABAA receptors restored LTP and memory encoding in females to levels as before puberty.

“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,” said Dr. Gail.

Further research will be conducted to determine if the sex-specific LTP threshold changes identified in the hippocampus during the transition to post-pubertal life are evident in other brain areas and influence the encoding of different types of memories.