Hardware versus software for mouse motor cortex action
The extent to which movements are mapped by cortical to spinal cord hard wiring versus the properties of less constrained cortical synaptic networks (software) is unclear. Using light to selectively activate the output neurons of mouse motor cortex we show that cortical areas can be biased for general types of limb movement; however the execution of complex movements was dependent on the action of intracortical synaptic activity. An understanding of the regulation of movement will aid the development of new treatments for disorders of the motor and sensory systems.
HFSP Program Grant holder Timothy Murphy and colleaguesauthored on Tue, 19 June 2012
The motor cortex has long been known to play a central role in the generation of movement, but fundamental questions remain about the functional organization of its subregions and their neuronal circuits. Results from electrical brain stimulation have traditionally been interpreted with an emphasis on a cortical body map, but the utility of this principle has diminished with the discovery of multiple representations of the body that could overlap in cortical space. Despite the detailed knowledge gleaned from these efforts, our understanding of the macroscopic organization of motor cortex remains incomplete. Much of our understanding about the motor cortex comes from experiments in which stimulation or recording is performed at a few cortical points. Recently, we and others have developed a novel method for rapid automated multi-point motor mapping based on light activation of the recombinant ion channel Channelrhodopsin-2. We apply light-based motor mapping to investigate the functional subdivisions of the motor cortex and their dependence on intracortical synaptic activity.
Figure: Upper image shows setup for movement measurement and mouse laser brain stimulation. Center left image shows cortical targets where Channelrhodopsin-2 stimulation was performed. Center right image show examples of general movement direction bias over the cortical surface, abduction versus adduction areas indicated. Lower image shows an example of a complex movement evoked by prolonged stimulation.
The ability to repeatedly map the motor cortex over timescales ranging from minutes to months has allowed us to appreciate the dynamic nature of movement representations and facilitated the comparison of motor maps generated before and after pharmacological perturbations of the intracortical circuitry. We have exploited the predominant expression of Channelrhodopsin-2 in layer 5 pyramidal neurons of Thy-1 transgenic mice to target this class of cortical output cells directly, exposing their contribution to motor cortex topography and identifying a functional subdivision of the mouse forelimb representation based on general movement direction. Prolonged trains of light or electrical stimulation revealed that activation of these subregions drives movements to distinct positions in space. To identify mechanisms that could account for the different movement types evoked by stimulation of these cortical subregions, we performed pharmacological manipulations of the intracortical circuitry and targeted anatomical tracing experiments.
Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography (directional bias of movement), but the site-specific expression of complex movements was lost. Our data suggest that the topography of movement maps arises from their hard-wired segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission.
This study helps to address the question of how motor cortex specificity is derived from a distributed network that was a subject of our 2010 HFSP Program Grant “Optical interrogation of motor cortex to provide insight into neuronal control of movement.” This work was facilitated by interactions between the trainee T. Harrison and HFSP Program Grant co-applicants E. Boyden and K. Martin. The interaction with Dr. Boyden was critical to apply fiber optic light stimulation technology to living mice necessary to activate sub-divisions of motor cortex. Dr. Martin provided valuable feedback during early stages of the project to T. Harrison, and ongoing collaborations will further investigate hard-wiring of motor cortex.
Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography. Harrison TC, Ayling OG, Murphy TH. Neuron. 2012 Apr 26;74(2):397-409.