Synaptic Basis for Whisker Deprivation-Induced Synaptic Depression in Rat Somatosensory Cortex

Abstract

Whisker deprivation weakens excitatory layer 4 (L4) inputs to L2/3 pyramidal cells in rat primary somatosensory (S1) cortex, which is likely to contribute to whisker map plasticity. This weakening has been proposed to represent long-term depression (LTD) induced by sensory deprivation in vivo. Here, we studied the synaptic expression mechanisms for deprivation-induced weakening of L4-L2/3 inputs and assessed its similarity to LTD, which is known to be expressed presynaptically at L4-L2/3 synapses. Whisker deprivation increased the paired pulse ratio at L4-L2/3 synapses and slowed the use-dependent block of NMDA receptor currents by MK-801 [(5S,10R)-(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], indicating that deprivation reduced transmitter release probability at these synapses. In contrast, deprivation did not alter either miniature EPSC amplitude in L2/3 neurons or the amplitude of quantal L4-L2/3 synaptic responses measured in strontium, indicating that postsynaptic responsiveness was unchanged. In young postnatal day 12 (P12) rats, at least 4 d of deprivation were required to significantly weaken L4-L2/3 synapses. Similar weakening occurred when deprivation began at older ages (P20), when synapses are mostly mature, indicating that weakening is unlikely to represent a failure of synaptic maturation but instead represents a reduction in the strength of existing synapses. Thus, whisker deprivation weakens L4-L2/3 synapses by decreasing presynaptic function, similar to known LTD mechanisms at this synapse.

Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex

“…In contemporaneous experiments, Bender et al (15,31) showed in layer 2/3 neurons of rat barrel cortex that STD-LTD, also occluded by whisker deprivation, is similarly inhibited by APV and AM251. Thus, a reasonable conclusion is that LFS and spike-timing protocols induce layer 2/3 LTD in sensory cortex by a common mechanism that is also accessed by sensory deprivation.…”

“…Thus, a reasonable conclusion is that LFS and spike-timing protocols induce layer 2/3 LTD in sensory cortex by a common mechanism that is also accessed by sensory deprivation. However, Bender et al (15,31) showed that intracellular MK801 (1 mM) had no effect on STD-LTD induction, whereas it was blocked by antagonists of metabotropic glutamate receptor 5 (mGluR5). They conclude that the relevant source of postsynaptic calcium for induction of STD-LTD is release from intracellular stores.…”

“…Second, as we show here, LFS-LTD is reliably blocked by intracellular MK801 (500 M). As a control for the possibility that MK801 might have leaked out of our recording pipette to affect presynaptic NMDARs implicated in STD-LTD, we repeated the experiments of Bender et al (15,31) using their spike-timing protocol in visual cortex of juvenile mice (Fig. 2).…”

Synapse-type-specific plasticity in local circuits

“…Conversely, sensory deprivation alters STP at a variety of synapses. However, the effect of sensory deprivation on STP is often inconsistent even for the same synapse type, with specific types of sensory deprivation promoting facilitation but others increasing depression [31 •• , [39][40][41][42][43]. A number of experimental factors, including the nature and age of deprivation [39,44] Similarly, preNMDARs influence STP at synapses from L4 neurons onto L2/3 pyramidal neurons, but not at L2/3 intralaminar synapses [47].…”

Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome

“…3F), the time constant of which is inversely related to P r . The decay kinetics were fit by a double exponential, and the fast time-constant of decay (τ f ) compared across groups (26,27). MK-801 blockade led to a slower τ f , implying a lower P r in KO cells [WT: 0.78 ± 0.32, n = 7; KO: 1.86 ± 0.24, n = 7 (stimuli); P < 0.05] (Fig.…”