Experience-Dependent Plasticity of Adult Rat S1 Cortex Requires Local NMDA Receptor Activation

Abstract

The effect of blocking NMDA glutamate receptors in adult rat cortex on experience-dependent synaptic plasticity of barrel cortex neurons was studied by infusing D-AP5 with an osmotic minipump over barrel cortex for 5 d of novel sensory experience. In acute pilot studies, 500 microM D-AP5 was shown to specifically suppress NMDA receptor (NMDAR)-dependent responses of single cells in cortical layers I-IV. To induce plasticity, all whiskers except D2 and D1 were cut close to the face 1 d after pump insertion. The animals were housed with 2 cage mates before recording 4 d later. This pairing of two whiskers for several days in awake animals generates highly significant biases in responses from D2 layer IV (barrel) cells to the intact D1 whisker as opposed to the cut D3 whisker. D-AP5 completely prevented the D1/D3 surround whisker bias from occurring in the D2 barrel cells (p > 0.6 for D1 > D3, Wilcoxon). Fast-spike and slow-spike barrel cells were affected equally, suggesting parity for inhibitory and excitatory cell plasticity. D-AP5 only partially suppressed the D1/D3 bias in supragranular layers (layers II-III) in the same penetrations (p < 0.042 for D1 > D3). In control animals, the inactive L-AP5 isomer allowed the bias to develop normally toward the intact surround whisker (p < 0.001 for D1 > D3) for cells in all layers. We conclude that experience-dependent synaptic plasticity of mature barrel cortex is cortically dependent and that modification of local cortical NMDARs is necessary for its expression.

Synaptic homeostasis and input selectivity follow from a calcium-dependent plasticity model

“…Analysis and simulations have shown that this model can explain the rate-, voltage-, and spike timing-dependent plasticity as consequences of, respectively, the temporal integration of calcium transients, the voltage-dependence of NMDAR conductances, and the coincidence-detection property of these receptors (3,5). In addition, numerous experimental results support the idea that NMDARs play key roles in activity-dependent development and refinement of synapses because of their permeability to calcium ions (6)(7)(8)(9)(10)(11).…”

α4* Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex

“…Although it is certain that cortical depression takes place, the molecular mechanisms that mediate this form of plasticity are not well understood, especially for adult animals that are less well studied. Thus far, mechanistic studies conducted primarily in young animals have implicated glutamate (Rema et al, 1998;Takahashi et al, 2003;Clem et al, 2008;Wright et al, 2008;Dachtler et al, 2011) and cannabinoid (L. ) receptor signaling in experience-based cortical depression. This leaves open the possibility that other modulators of synaptic signaling, perhaps acting through inhibitory circuits which have recently been implicated in visual (Yazaki-Sugiyama et al, 2009) and barrel cortex plasticity (Jiao et al, 2006;Sun, 2009) may be involved.…”

Mechanisms of use-dependent plasticity in the human motor cortex

“…Specifically, we tested the effects on use-dependent plasticity of (i) lorazepam (LZ), a drug that enhances ␥-aminobutyric acid type A (GABA A ) receptor function by acting as a positive allosteric modulator (12) and that blocks the induction of LTP (10); (ii) dextromethorphan (DM), a drug that blocks N-methyl-Daspartate (NMDA) receptors (11,13), required for LTP in the motor cortex (7,11), and experience-dependent plasticity in the somatosensory cortex (14); and (iii) lamotrigine (LG), a drug that modifies the gating of voltage-activated Na ϩ and Ca 2ϩ channels (15) without affecting LTP induction (16,17).…”