Presynaptic ionotropic receptors and control of transmitter release

140

138

Presynaptic NMDA receptors (NMDARs) modulate release and plasticity at many glutamatergic synapses, but the specificity of their expression across synapse classes has not been examined. We found that non-postsynaptic, likely presynaptic NR2B-containing NMDARs enhanced AMPA receptor-mediated synaptic transmission at layer 4 (L4) to L2/3 (L4 -L2/3) synapses in juvenile rat barrel cortex. This modulation was apparent at room temperature when presynaptic NMDARs were activated by elevation of extracellular glutamate or application of exogenous NMDAR agonists. At near physiological temperatures, modulation of transmission by presynaptic NMDARs occurred naturally, without the need for external activation. Blockade of presynaptic NMDARs depressed unitary and extracellularly evoked EPSCs at L4 -L2/3 synapses, accompanied by increases in paired-pulse ratio and coefficient of variation, indicative of a decrease in presynaptic release probability. NMDAR agonists increased the frequency of miniature EPSCs in L2/3 neurons, without altering their amplitude or kinetics. Focal application of NMDAR antagonist revealed that the NMDARs that modulate L4 -L2/3 transmission are located in L2/3, not L4, consistent with localization on terminals or axons of L4 -L2/3 synapses, rather than on the somatodendritic compartment of presynaptic L4 neurons. In contrast, presynaptic NMDARs did not modulate L4 -L4 synapses, which originate from the same presynaptic neurons as L4 -L2/3 synapses, or cross-columnar L2/3-L2/3 horizontal projections, which synapse onto the same postsynaptic target neurons. Thus, presynaptic NMDARs selectively modulate L4 -L2/3 synapses, relative to other synapses made by the same neurons. Existence of these receptors may support specialized processing or plasticity by L4 -L2/3 synapses.

Section: Introductionmentioning

confidence: 99%

Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex

Brasier¹,

Feldman²

2008

140

138

“…However, glutamate receptors, including NMDARs, have also been found on the presynaptic terminals of GABAergic neurons (Belan and Kostyuk, 2002). Activation of these glutamate receptors can transiently enhance or suppress the release of GABA from inhibitory interneurons (Engelman and MacDermott, 2004). Whether glutamate can produce a lasting enhancement of the release of transmitters from inhibitory neurons remains mostly unknown.…”

Section: Introductionmentioning

confidence: 99%

The Activation of Excitatory Glutamate Receptors Evokes a Long-Lasting Increase in the Release of GABA from Cerebellar Stellate Cells

Liu

Lachamp²

2006

The excitability of a neuron is regulated by the balance of excitatory and inhibitory inputs that impinge on it. Such modulation can occur either presynaptically or postsynaptically. Here, we show that an excitatory transmitter can increase the release of an inhibitory transmitter and thus paradoxically produces a long-lasting enhancement of inhibitory synaptic transmission. This occurs at a nearphysiological temperature. These findings from cerebellar stellate neurons reveal a novel form of long-term potentiation that is induced by the activation of NMDA-type glutamate receptors and that requires both glutamate and glycine. Our results indicate that Ca 2ϩ entry into the presynaptic terminals during the activation of presynaptic NMDARs is necessary to induce the potentiation. This presynaptic modulation provides a mechanism by which an excitatory transmitter can induce a long-term increase in the release of an inhibitory transmitter and thus modify the activity of a simple neuronal circuit.

“…␣7 nAChRs are pentameric ligand-gated cation channels distinguished by a high relative permeability to Ca 2ϩ (Seguela et al, 1993;Fucile, 2004), enabling ␣7 nAChRs to exert diverse modulatory influences via Ca 2ϩ -dependent cellular mechanisms (Dajas-Bailador and Wonnacott, 2004). ␣7 nAChRs have been implicated in the modulation of glutamate release in several brain regions, in addition to the VTA (Engelman and MacDermott, 2004), including the hippocampus (Gray et al, 1996), olfactory bulb (Alkondon et al, 1996), and sensory cortex (Aramakis and Metherate, 1998). In these studies, the Ca 2ϩ dependence and tetrodotoxin insensitivity of nicotinic mechanisms implied that ␣7 nAChRs are located on glutamatergic axon terminals.…”

Section: Introductionmentioning

confidence: 99%

Precise Localization of α7 Nicotinic Acetylcholine Receptors on Glutamatergic Axon Terminals in the Rat Ventral Tegmental Area

Jones¹,

Wonnacott²

2004

253

214

␣7 neuronal nicotinic acetylcholine receptors (nAChRs) constitute one of the predominant nAChR subtypes in the mammalian brain. Within the ventral tegmental area (VTA), nicotine application, paired with postsynaptic stimulation, contributes to a form of long-term potentiation, an effect attributed to presynaptic ␣7 nAChRs on glutamatergic afferents (Mansvelder and McGehee, 2000). The aim of this study was to examine the precise subcellular distribution of ␣7 nAChRs in the adult rat VTA to establish whether these receptors are indeed present on glutamatergic axon terminals and to determine their relationship with cholinergic afferents. The spatial relationship between ␣7 nAChRs, labeled using the ␣7 nAChR-specific antagonist ␣-bungarotoxin, and the local neurochemical environment was investigated by the application of multiple labeling strategies with antibodies against tyrosine hydroxylase, vesicular glutamate transporters (VGluTs), vesicular acetylcholine transporter, and glial fibrillary acidic protein. ␣7 nAChRs were localized at both somatodendritic and presynaptic loci within the VTA: on subpopulations of dopaminergic and nondopaminergic neurons and glutamatergic and nonglutamatergic terminals. There was no detectable ␣7 nAChR expression within astrocytes in the VTA. Most ␣7 nAChRs were cytoplasmic (82%), and the remainder were associated with the plasma membrane. Most presynaptic receptors (75%) were on glutamatergic axon terminals, with similar levels of ␣-bungarotoxin binding present on both VGluT1-and VGluT2-immunoreactive boutons. Both preembedding and postembedding electron microscopy revealed that presynaptic ␣7 nAChRs are often located at extrasynaptic (27%) and perisynaptic (61%) loci. ␣7 nAChRs were not associated with cholinergic synapses, consistent with their activation by a paracrine mode of acetylcholine or choline delivery.