Identification of an axonal determinant in the C-terminus of the sodium channel Na(v)1.2.

To obtain a better understanding of how hippocampal neurons selectively target proteins to axons, we assessed whether any of the large cytoplasmic regions of neuronal sodium channel Na(v)1.2 contain sufficient information for axonal compartmentalization. We show that addition of the cytoplasmic C-terminal region of Na(v)1.2 restricted the distribution of a dendritic-axonal reporter protein to axons. The analysis of mutants revealed that a critical segment of nine amino acids encompassing a di-leucine-based motif mediates axonal compartmentalization of chimera. In addition, the Na(v)1.2 C-terminus is recognized by the clathrin endocytic pathway both in non-neuronal cells and the somatodendritic domain of hippocampal neurons. The mutation of the di-leucine motif located within the nine amino acid sequence to alanines resulted in the loss of chimera compartmentalization in axons and of internalization. These data suggest that selective elimination by endocytosis in dendrites may account for the compartmentalized distribution of some proteins in axons.

The chronometry of single neuron activity: testing discrete and continuous models of information processing.

The authors propose to study information transmission by comparing the effects of experimental factors on reaction time (RT) with the latency of the changes in activity of single-neurons. An experiment was conducted in which a monkey (Macaca mulatta) performed a tactilo-manual 2-choice RT task and the compatibility of the stimulus-response mapping was manipulated. Task-related neurons were recorded in the monkey's primary somesthetic and motor cortices. The changes in activity of 105 of these neurons were classified either as sensory-like or as motor-like. The sensory-like changes occurred before the motor-like ones. The stimulus-response mapping exerted its entire effect on the RT after the sensory-like changes and before the motor-like ones. These findings suggest that the information was transmitted discretely from the processes affected by the mapping to the processes implemented by the motor-like changes.

Cortico-spinal inhibition reflects time but not event preparation: neural mechanisms of preparation dissociated by transcranial magnetic stimulation.

Changes in cortico-spinal excitability related to time and event preparation were investigated by transcranial magnetic stimulation (TMS) of the motor cortex during the foreperiod of a movement-precuing task. Subjects performed a four alternative choice reaction time (RT) task involving a button-press with the index or middle finger (FI) of the left or right hand. Advance information about the to-be-signaled response was provided by a precue, which preceded the response signal by a 1 s foreperiod. The precue either indicated the hand (right or left) or FI (index or middle) with which the response would be executed or was uninformative. TMS was delivered to the left or right cortical hand area at one of five possible times during the foreperiod: -1000, -500, -333, -166 or 0 ms prior to the response signal. Surface EMG activity from a prime mover involved in flexion of the response FIs (Flexor digitorum superficialis) was used to measure the magnitude of the motor evoked potential (MEP) elicited by TMS. Cortico-spinal excitability--as assessed by the magnitude of the MEP evoked in the target muscle contralateral to the stimulated hemisphere--progressively decreased during the foreperiod. The identity of the precued responses, however, had no effect on MEP magnitude. These results suggest that preparation to respond at a particular time inhibited excitability of the cortico-spinal tract, while advance preparation to perform specific responses affected more central structures only.

Why does the single neuron activity change from trial to trial during sensory-motor task?

Single neuron activities from cortical areas of a monkey were recorded while performing a sensory-motor task (a choice reaction time task). Quantitative trial-by-trial analysis revealed that the timing of peak activity exhibited large variation from trial to trial, compared to the variation in the behavioral reaction time of the task. Therefore, we developed a multi-unit dynamic neural network model to investigate the effects of structure of neural connections on the variation of the timing of peak activity. Computer simulation of the model showed that, even though the units are connected in a cascade fashion, a wide variation exists in the timing of peak activity of neurons because of parallel organization of neural network within each unit.

Finger Pairings in Two-Choice Reaction Time Taskscolon: Does the Between-Hands Advantage Reflect Response Preparation?

Two fractionated RT experiments tested whether the response-preparation or response-implementation hypothesis better accounts for the observation that two-choice reaction time (RT) usually takes longer when the responses are performed by the fingers of the same hand (within-hand repertoire) than by the fingers of the two hands (between-hands repertoire). In Experiment I (n equals 8), the effect of repertoire on the premotor time and the motor time were studied. RT was divided into the two periods with respect to the onset of change in electromyographic (EMG) activity of the flexor digitorum profundus. Type of repertoire affected both time periods. In Experiment 2 (n = 16), the effects of repertoire and foreperiod duration on the premotor and motor times of the flexor digitorum profundus and flexor digitorum sublimis were studied. The results of Experiment I were confirmed, and the effects of repertoire and foreperiod duration were found to be additive on premotor time but interactive on motor time. These findings led to rejection of the response-preparation hypothesis and instead supported the view that the central command for the flexion of the right middle finger differs according to the type of repertoire. The command appears to specify a lower rate of recruitment of the prime movers in the within-hand repertoire than in the between-hands repertoire. The execution of the central commands may depend on the state of excitability of the spinal neurons. Analysis of the EMG signals revealed that speed of contraction of the prime movers depends on repertoire when the foreperiod is long but not when it is short. The additivity of the effects of repertoire and of foreperiod duration on premotor time support the view that regardless of the state of preparation of the subject the pattern of EMG activity required for flexion of the right middle finger in each repertoire is specified during the premotor time.