Sex differences in synaptic plasticity underlying learning
- 12 April 2021
- journal article
- review article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 101 (5), 764-782
- https://doi.org/10.1002/jnr.24844
Abstract
Although sex differences in learning behaviors are well documented, sexual dimorphism in the synaptic processes of encoding is only recently appreciated. Studies in male rodents have built upon the discovery of long‐term potentiation (LTP), and acceptance of this activity‐dependent increase in synaptic strength as a mechanism of encoding, to identify synaptic receptors and signaling activities that coordinate the activity‐dependent remodeling of the subsynaptic actin cytoskeleton that is critical for enduring potentiation and memory. These molecular substrates together with other features of LTP, as characterized in males, have provided an explanation for a range of memory phenomena including multiple stages of consolidation, the efficacy of spaced training, and the location of engrams at the level of individual synapses. In the present report, we summarize these findings and describe more recent results from our laboratories showing that in females the same actin regulatory mechanisms are required for hippocampal LTP and memory but, in females only, the engagement of both modulatory receptors such as TrkB and synaptic signaling intermediaries including Src and ERK1/2 requires neuron‐derived estrogen and signaling through membrane‐associated estrogen receptor α (ERα). Moreover, in association with the additional ERα involvement, females exhibit a higher threshold for hippocampal LTP and spatial learning. We propose that the distinct LTP threshold in females contributes to as yet unappreciated sex differences in information processing and features of learning and memory.Keywords
Funding Information
- Office of Naval Research
- National Institute of Mental Health (5T32MH119049‐02)
- National Institutes of Health (NS045260, NS085709, HD089491)
This publication has 174 references indexed in Scilit:
- Synaptic evidence for the efficacy of spaced learningProceedings of the National Academy of Sciences of the United States of America, 2012
- The likelihood of cognitive enhancementPharmacology Biochemistry and Behavior, 2011
- Myosin IIb Regulates Actin Dynamics during Synaptic Plasticity and Memory FormationNeuron, 2010
- Estradiol and the relationship between dendritic spines, NR2B containing NMDA receptors, and the magnitude of long-term potentiation at hippocampal CA3–CA1 synapsesPsychoneuroendocrinology, 2009
- 17-β-Estradiol increases neuronal excitability through MAP kinase-induced calpain activationProceedings of the National Academy of Sciences of the United States of America, 2009
- The Episodic Memory System: Neurocircuitry and DisordersNeuropsychopharmacology, 2009
- Modulation of long-term memory for object recognition via HDAC inhibitionProceedings of the National Academy of Sciences of the United States of America, 2009
- Effects of neonatal (+)-methamphetamine on path integration and spatial learning in rats: effects of dose and rearing conditionsInternational Journal of Developmental Neuroscience, 2008
- Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement taskNeurobiology of Learning and Memory, 2007
- Integrins: Versatility, modulation, and signaling in cell adhesionCell, 1992