Developmental restoration of LTP deficits in heterozygous CaMKIIα KO mice.

J Neurophysiol

Department of Pharmacology and Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, Colorado; and

Published: November 2016

The Ca/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. The heterozygous CaMKIIα isoform KO (CaMKIIα) mice have a schizophrenia-related phenotype, including impaired working memory. Here, we examined synaptic strength and plasticity in two brain areas implicated in working memory, hippocampus CA1 and medial prefrontal cortex (mPFC). Young CaMKIIα mice (postnatal days 12-16; corresponding to a developmental stage well before schizophrenia manifestation in humans) showed impaired hippocampal CA1 LTP. However, this LTP impairment normalized over development and was no longer detected in older CaMKIIα mice (postnatal weeks 9-11; corresponding to young adults). By contrast, the CaMKIIα mice failed to show the developmental increase of basal synaptic transmission in the CA1 seen in wild-type (WT) mice, resulting in impaired basal synaptic transmission in the older CaMKIIα mice. Other electrophysiological parameters were normal, including mPFC basal transmission, LTP, and paired-pulse facilitation, as well as CA1 LTD, depotentiation, and paired-pulse facilitation at either age tested. Hippocampal CaMKIIα levels were ∼60% of WT in both the older CaMKIIα mice and in the younger WT mice, resulting in ∼30% of adult WT expression in the younger CaMKIIα mice; levels in frontal cortex were the same as in hippocampus. Thus, in young mice, ∼30% of adult CaMKIIα expression is sufficient for normal LTD and depotentiation, while normal LTP requires higher levels, with ∼60% of CaMKIIα expression sufficient for normal LTP in adult mice.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102309PMC
http://dx.doi.org/10.1152/jn.00518.2016DOI Listing

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