Activation of AMPA, Kainate, and Metabotropic Receptors at Hippocampal Mossy Fiber Synapses

Abstract

Glutamatergic transmission at mossy fiber (MF) synapses on CA3 pyramidal neurons in the hippocampus is mediated by AMPA, kainate, and NMDA receptors and undergoes presynaptic modulation by metabotropic glutamate receptors. The recruitment of different receptors has thus far been studied by altering presynaptic stimulation to modulate glutamate release and interfering pharmacologically with receptors and transporters. Here, we introduce two novel experimental manipulations that alter the fate of glutamate molecules following release. First, an enzymatic glutamate scavenger reduces the postsynaptic response as well as presynaptic modulation by metabotropic receptors. At physiological temperature, however, the scavenger is effective only when glutamate uptake is blocked, revealing a role of active transport in both synaptic and extrasynaptic communication. Second, AMPA and kainate receptor-mediated postsynaptic signals are enhanced when extracellular diffusion is retarded by adding dextran to the perfusion solution, as is feedback modulation by metabotropic receptors, suggesting that the receptors are not saturated under baseline conditions. These results show that manipulating the spatiotemporal profile of glutamate following exocytosis can alter the involvement of different receptors in synaptic transmission.

Hallucinogen-Induced UP States in the Brain Slice of Rat Prefrontal Cortex: Role of Glutamate Spillover and NR2B-NMDA Receptors

“…These late EPSCs are selectively suppressed by increasing the viscosity of the extracellular space, a manipulation known to retard extrasynaptic transmission (Min et al, 1998;Perrais and Ropert, 2000;Nielsen et al, 2004). They also depend on NR2B-containing NMDA receptors, a population thought to be mainly extrasynaptic in the adolescent and adult rat (Stocca and Vicini, 1998;Rumbaugh and Vicini, 1999;Tovar and Westbrook, 1999;Townsend et al, 2003;Liu et al, 2004).…”

“…Drugs were obtained from Sigma (St Louis, MO). The dextran solution was prepared according to previously established methods (Min et al, 1998;Nielsen et al, 2004). Dextran (B40 kDa) was added to standard ACSF in a concentration of 5% and rendered iso-osmotic by diluting the solution with water (B6%).…”

“…First, we retard the diffusion of glutamate beyond the synapse by changing the viscosity of the extracellular space using dextran, a macromolecule that has often been employed to suppress spillover (Min et al, 1998;Perrais and Ropert, 2000;Nielsen et al, 2004;Piet et al, 2004;Savtchenko and Rusakov, 2005). Then, we assess the subtypes of NMDA receptors that are involved in the delayed wave of glutamate enhanced by psychedelic hallucinogens.…”

The mGluR2/3 Agonist LY379268 Blocks the Effects of GLT-1 Upregulation on Prepulse Inhibition of the Startle Reflex in Adult Rats

“…Owing to its perisynaptic localization (Rusakov and Lehre, 2002;Melone et al, 2009a), GLT-1 regulates glutamate spillover, thereby modulating the activation of glutamate receptors (Scanziani et al, 1997;Min et al, 1998;Mitchell and Silver, 2000;Tzingounis and Wadiche, 2007).…”

Metabotropic glutamate receptor-mediated hetero-synaptic interaction of red- and green-cone inputs to LHC of carp retina

“…transmitters released from one synapse lead to significant activation of receptors at an adjacent synapse and modulate its synaptic transmission [21]. For excitatory glutamatergic synaptic contact, especially, glutamate may spill over from the synaptic cleft and diffuse to activate extrasynaptic receptors on presynaptic and/or postsynaptic membrane [14]. Activation of mGluRs may suppress the glutamate release from the presynaptic terminals, which was thought to mediate the hetero-synaptic repression between distinct synapse [15].…”