Do the interim KRX-0401 in vitro lessons drawn from the study of motor system circuitry and function have a broader relevance—to the challenges inherent in linking neural organization to encoded behavior? Several thoughts suggest themselves. First and foremost, motor systems offer the singular virtue of a rather direct link

between the organization of a neural circuit and its behavioral output—in this case, patterned muscle contraction. In the case of the motor neuron, its muscle target soon becomes a fixed and inseparable component of the “motor unit,” such that much of the neural computation inherent in the CNS is involved with the planning and execution of spinal motor programs. Understanding how the behaviors Tyrosine Kinase Inhibitor Library research buy encoded by other CNS circuits impinge on core motor routines could lead to more objective and quantitative ways of evaluating the world of complex behavior. Studies of spinal motor neurons have also served to remind us of the primacy of limb biomechanics in assigning functional order to motor circuits. Along the way,

these studies have revealed that the location of a motor neuron or interneuron in the spinal cord constrains many of its potential connections, permitting some and excluding others. It may be worthwhile considering whether this positional principle extends beyond the spinal cord, and beyond the motor system. The prominence of nuclear organization as a means of positioning neurons throughout the subcortical CNS, together with

the critical influence of neuronal settling position in defining patterns of sensory input connectivity, suggests that position may be a crucial determinant of connectivity throughout the vertebrate CNS. The trick in testing this assertion is the accumulation of sufficient molecular information on neuronal subtype to alter settling position without eroding core identity, and examine the subsequent impact on connectivity and behavior. In the motor see more system as elsewhere, neuronal circuit models commonly suffer the weakness of being poorly constrained by existing information on connectivity within and between neuronal populations. When pursued alone, even the most contemporary methods for inferring circuit architecture from activity measurements fail to specify unambiguously the underlying circuit mechanisms that biology implements. In the same way that methodological advances in structural biology have helped to trim a seeming infinity of plausible protein models, we anticipate that increasingly detailed circuit mapping will produce constraints on neuronal circuit models that sharpen our understanding of their functional architecture. A final inference to be drawn from this motor system precedent is that there may be considerable mileage to be gained from studies of the intersection of anatomically separable regions devoted to the control of a given behavior.