A Single Brief Burst Induces GluR1-dependent Associative Short-term Potentiation: A Potential Mechanism for Short-term Memory

Abstract

Recent work [Sanderson, D., Good, M.A., Skelton, K., Sprengel, R., Seeburg, P. H., Nicholas, J., et al. Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: Evidence for a dual-process memory model. Learning and Memory, in press] showed that short-term memory (STM) is selectively reduced in GluR1 knockout mice. This raises the possibility that a form of synaptic modification dependent on GluR1 might underlie STM. Studies of synaptic plasticity have shown that stimuli too weak to induce long-term potentiation induce short-term potentiation (STP), a phenomenon that has received little attention. Here we examined several properties of STP and tested the dependence of STP on GluR1. The minimal requirement for inducing STP was examined using a test pathway and a conditioning pathway. Several closely spaced stimuli in the test pathway, forming a single brief burst, were sufficient to induce STP. Thus, STP is likely to be induced by the similar bursts that occur in vivo. STP induction is associative in nature and dependent on the NMDAR. STP decays with two components, a fast component (1.6 ± 0.26 min) and a slower one (19 ± 6.6 min). To test the role of GluR1 in STP, experiments were conducted on GluR1 knockout mice. We found that STP was greatly reduced. These results, taken together with the behavioral work of D. Sanderson et al. [Sanderson, D., Good, M. A, Skelton, K., Sprengel, R., Seeburg, P. H., Nicholas, J., et al. Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: Evidence for a dual-process memory model. Learning and Memory, in press], provide genetic evidence that STP is a likely mechanism of STM.

Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

“…Although not widely considered, STP is a strong candidate mechanism for some forms of working memory, a mechanism that could complement the persistent firing that is often viewed as the sole mechanism of working memory. Consistent with an important role for STP in working memory, experiments on GluA1 knockout (KO) mice show a profound decrement in both STP [2] and working memory [3].…”

Hippocampal synaptic plasticity, spatial memory and anxiety

“…The GluA1 subunit is thought to play an important role in aspects of AMPAR trafficking 135,136 and in mechanisms underlying synaptic plasticity, particularly short-term forms of plasticity 130,[137][138][139] . GluA1 is also important for SWM performance 20,129,140 .…”

Impaired Path Integration and Grid Cell Spatial Periodicity in Mice Lacking GluA1-Containing AMPA Receptors

“…Although GluA1 Ϫ/Ϫ mice lack the GluA1 subunit constitutively, they develop normally and their life expectancy is unchanged. In the hippocampus, the lack of GluA1 in mutant mice leads to a decreased number of functional AMPA receptors and deficits in forms of short-lasting synaptic plasticity (Zamanillo et al, 1999;Hoffman et al, 2002;Romberg et al, 2009;Erickson et al, 2010). Place cells in GluA1 Ϫ/Ϫ mice exhibit reduced spatial selectivity, supporting the notion that hippocampal spatial representations are altered in these mice (Resnik et al, 2012).…”