The functional organization of motor cortex: development, circuitry and plasticity

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How is it that memories are encoded into the brain? Most behavioural neuroscientists agree that memories are instantiated in the brain through changes in the connection strengths between neurons which in turn causes a restructuring of neural circuits. I am intensely interested in this “synaptic plasticity and memory hypothesis” and I choose to explore it within the mammalian motor cortex. The motor cortex is a highly amenable structure to investigate. The output of motor cortex is behaviour which can be directly observed and measured. Motor representations, also known as motor maps, are related to behavioural functioning, topographically organized, provide a wealth of information and can be experimentally manipulated. Finally networks of neurons within layer V make synaptic connections with pyramidal neurons that we can manipulate and measure in vitro with an extraordinary high degree of experimental control. Thus, I propose to analyze the functioning of motor cortex at three inter-related levels of analysis; a) behaviour of the forelimb, b) motor representations (motor maps) of the forelimb using both short- and long-train intracortical microstimulation which give rise to standard and complex motor maps respectively, and c) by examining the electrophysiological properties of layer V pyramidal cells using an in vitro slice preparation that we have developed. I will advance our knowledge of learning and memory by determining; a) the consequences of experience on development, b) the role of the areas of motor cortex specialized for complex movements and in the learning of skilled behaviours, c) the anatomical relationship between areas of cortex and the representations of complex movements, as well as whether there is anatomical segregation in the thalamus and spinal cord, and d) the role of endocannabinoids on skilled learning and the expression of motor maps. There are several new innovations that my laboratory incorporates. We have adapted a cortical cooling methodology that allows us to selectively and reversibly inactivate specific areas on motor cortex both in acute and chronic preparations. We perform both standard (short) and long-train intracortical microstimulation techniques to derive motor maps in rats and genetically modified mouse strains. We have developed a slice preparation from motor cortex that recapitulates the essential features of intracortical microstimulation and allows for an in depth electrophysiological analysis of the output layer of motor cortex. Perhaps most importantly all of these methodologies are performed within the same laboratory and will allow us to achieve a better understanding of the mechanisms responsible for learning and memory in the mammalian neocortex.