Theory for normal and impaired experience-dependent plasticity in neocortex of adult rats.

We model experience-dependent plasticity in the cortical representation of whiskers (the barrel cortex) in normal adult rats, and in adult rats that were prenatally exposed to alcohol. Prenatal exposure to alcohol (PAE) caused marked deficits in experience-dependent plasticity in a cortical barrel-column. Cortical plasticity was induced by trimming all whiskers on one side of the face except two. This manipulation produces high activity from the intact whiskers that contrasts with low activity from the cut whiskers while avoiding any nerve damage. By a computational model, we show that the evolution of neuronal responses in a single barrel-column after this sensory bias is consistent with the synaptic modifications that follow the rules of the Bienenstock, Cooper, and Munro (BCM) theory. The BCM theory postulates that a neuron possesses a moving synaptic modification threshold, theta(M), that dictates whether the neuron's activity at any given instant will lead to strengthening or weakening of its input synapses. The current value of theta(M) changes proportionally to the square of the neuron's activity averaged over some recent past. In the model of alcohol impaired cortex, the effective theta(M) has been set to a level unattainable by the depressed levels of cortical activity leading to "impaired" synaptic plasticity that is consistent with experimental findings. Based on experimental and computational results, we discuss how elevated theta(M) may be related to (i) reduced levels of neurotransmitters modulating plasticity, (ii) abnormally low expression of N-methyl-d-aspartate receptors (NMDARs), and (iii) the membrane translocation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in adult rat cortex subjected to prenatal alcohol exposure.