Multiple forms of activity‐dependent intrinsic plasticity in layer V cortical neurones in vivo

Abstract

Synaptic plasticity is classically considered as the neuronal substrate for learning and memory. However, activity-dependent changes in neuronal intrinsic excitability have been reported in several learning-related brain regions, suggesting that intrinsic plasticity could also participate to information storage. Compared to synaptic plasticity, there has been little exploration of the properties of induction and expression of intrinsic plasticity in an intact brain. Here, by the means of in vivo intracellular recordings in the rat we have examined how the intrinsic excitability of layer V motor cortex pyramidal neurones is altered following brief periods of repeated firing. Changes in membrane excitability were assessed by modifications in the discharge frequency versus injected current (F-I) curves. Most (∼64%) conditioned neurones exhibited a long-lasting intrinsic plasticity, which was expressed either by selective changes in the current threshold or in the slope of the F-I curve, or by concomitant changes in both parameters. These modifications in the neuronal input-output relationship led to a global increase or decrease in intrinsic excitability. Passive electrical membrane properties were unaffected by the intracellular conditioning, indicating that intrinsic plasticity resulted from modifications of voltage-gated ion channels. These results demonstrate that neocortical pyramidal neurones can express in vivo a bidirectional use-dependent intrinsic plasticity, modifying their sensitivity to weak inputs and/or the gain of their input-output function. These multiple forms of experience-dependent intrinsic changes, which expand the computational abilities of individual neurones, could shape new network dynamics and thus might participate in the formation of mnemonic motor engrams.

Bidirectional Plasticity of Intrinsic Excitability Controls Sensory Inputs Efficiency in Layer 5 Barrel Cortex Neuronsin Vivo

“…Remarkably, we found that the same conditioning protocol could induce either LLPIE or LL-DIE in barrel cortex neurons in vivo. We recently made partly similar observations in motor cortex neurons in vivo where repeated injection of suprathreshold currents produced enduring increases or decreases in membrane excitability, which were associated with changes in both current threshold and neuronal gain (Paz et al, 2009). Here, we show that the variability in neuronal spontaneous firing rate, which is inherent to the living brain (Sachdev et al, 2004;Polack and Charpier, 2006;Jacob et al, 2007;Pidoux et al, 2011), could provide a significant determinant of the polarity of plasticity.…”

“…To generate firing frequency versus injected current ( F-I) relationships, the firing rate was measured in response to depolarizing current pulses of increasing intensity (500 ms, 0.1-1.4 nA) delivered with an interstimulus interval of 3.25-5.25 s. Each current intensity was applied 20 -25 times and the corresponding firing responses were averaged. As previously described (Paz et al, 2009), we applied linear regressions to F-I curves and determined the threshold current for AP generation, extrapolated as the x-intercept of the linear fit (Fig. 1D), and the neuronal gain, defined as the slope of the F-I curve.…”

“…By enhancing or depressing the responsiveness of individual neurons to incoming inputs, intrinsic plasticity can strongly affect the collective activity in neural networks (Marder and Prinz, 2002). Changes in cortical neuron excitability have been observed from ex vivo slices following learning procedures (Saar et al, 1998;Matthews et al, 2008) or after experimental manipulation of the levels of activity in vitro and in vivo (Desai et al, 1999;Sourdet et al, 2003;Cudmore and Turrigiano, 2004;Paz et al, 2009). Until now, intrinsic plasticity in barrel cortex neurons has been mainly studied in the context of brain maturation.…”

Intrinsic neuronal excitability: implications for health and disease

“…For example, in vivo, the input/output function of rat motor cortex neurons can be modified by conditioning with a short burst of APs (6). In vitro, this modification can be related to changes in the number or kinetics of voltage-gated ion channels present in the plasma membrane in a compartmentdependent manner (i.e., axon, soma, and dendrite).…”

Automatic abstraction and fault tolerance in cortical microachitectures

“…Note that weight normalizationWij(t) is a (simple) emulation of the "synaptic scaling" phenomenon observed in several regions of the brain [18] and that of the gain was inspired by the so-called "intrinsic plasticity" (i.e. activity dependent modification of the neuron gain) observed in the cortex [25]. T defines the robustness of a MC to noisy input and can take a value between 0 and 1.…”