Long-term potentiation and dual-component quantal signaling in the dentate gyrus

Abstract

Long-term potentiation (LTP) of excitatory transmission is an important candidate cellular mechanism for the storage of memories in the mammalian brain. The subcellular phenomena that underlie the persistent increase in synaptic strength, however, are incompletely understood. A potentially powerful method to detect a presynaptic increase in glutamate release is to examine the effect of LTP induction on the rate at which the use-dependent blocker MK-801 attenuates successive N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic signals. This method, however, has given apparently contradictory results when applied in hippocampal CA1. The inconsistency could be explained if NMDA receptors were opened by glutamate not only released from local presynaptic terminals, but also diffusing from synapses on neighboring cells where LTP was not induced. Here we examine the effect of pairing-induced LTP on the MK-801 blocking rate in two afferent inputs to dentate granule cells. LTP in the medial perforant path is associated with a significant increase in the MK-801 blocking rate, implying a presynaptic increase in glutamate release probability. An enhanced MK-801 blocking rate is not seen, however, in the lateral perforant path. This result still could be compatible with a presynaptic contribution to LTP in the lateral perforant path if intersynaptic cross-talk occurred. In support of this hypothesis, we show that NMDA receptors consistently sense more quanta of glutamate than do ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the medial perforant path, in contrast, there is no significant difference in the number of quanta mediated by the two receptors. These results support a presynaptic contribution to LTP and imply that differences in intersynaptic cross-talk can complicate the interpretation of experiments designed to detect changes in transmitter release.Long-term potentiation (LTP) is the foremost candidate cellular substrate for memory formation and also may play a major role in the development of neuronal circuits and in neuronal injury (1). In spite of intense effort, the underlying cellular mechanisms of expression remain a matter of some debate (2-4). A potentially sensitive method to detect an increase in presynaptic glutamate release probability is to examine the effect of LTP induction on the rate at which the use-dependent blocker MK-801 attenuates successive excitatory postsynaptic currents (EPSCs) mediated by N-methyl-D-aspartic acid (NMDA) receptors (5, 6). If glutamate is released on a higher proportion of trials after LTP induction, the NMDA receptor-gated channels should be activated more frequently, and MK-801 therefore should produce a faster reduction in the size of the synaptic signal. This method, however, has given conflicting results when applied in the CA1 region of the hippocampus. LTP induced by pairing low-frequency presynaptic stimulation with postsynaptic depolarization was associated with no significant increase in blocking rate (7). Significantly enhanced a...

LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

“…The mean EPSC synaptic transmission rate was 0.7 Ϯ 0.03 in granule cells from LIS1 mutants (n ϭ 11). Although ϳ50% eEPSC transmission failure observed in controls is comparable with previous reports (Min et al, 1998), response failures were less frequent in LIS1 mutants versus wild-type animals (p Ͻ 0.001, two-tailed t test). Together, these findings reveal that release probability at the perforant pathway-granule cell synapse is enhanced in LIS1 mutant mice.…”

Changes in extracellular space size and geometry in APP23 transgenic mice: A model of Alzheimer's disease

“…An increase in ECS volume leads to diminished extracellular-field potentials and reduced excitability in the neocortex (38). Glutamate and ␥-aminobutyric acid spillover and crosstalk between synapses, which depend critically on diffusion parameters, have been suggested to play a role in long-term potentiation and long-term depression (39,40). Therefore, the changes in ECS volume and ADC TMA observed in our study, the rearrangement of astrocytic processes, and amyloid plaques can contribute to behavioral deficits in severely affected APP23 females.…”

Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat

“…Variations in maternal care were associated with the response to paired-pulse stimulation in the medial perforant path, with a significantly greater depression of subsequent responding in slices from the adult offspring of high-LG compared with low-LG mothers. The medial perforant pathway is characterized by a very high glutamate release probability (44). Regulation of presynaptic glutamate release is therefore a highly effective mechanism in determining synaptic strength and plasticity, especially during repetitive stimulation of this pathway, while inducing synaptic plasticity.…”

“…When two identical stimulations are separated by a short interval (<1,000 ms), modification of the size of the response to the second pulse relative to the first pulse reflects homeostatic control of presynaptic glutamate release (43) and is the measure for paired-pulse depression (PPD). The medial perforant pathway of the dentate gyrus is characterized by a very high glutamate release probability (44), and in contrast to other hippocampal synapses, paired-pulse stimulation results in depression of the second pulse relative to the first (45). We examined regulation of PPD by mGluR1 in slices from high-and low-LG offspring.…”