Subject(s)
Blood-Brain Barrier/drug effects , Drug Delivery Systems/methods , Antineoplastic Agents/administration & dosage , Biological Transport , Blood-Brain Barrier/physiology , Drug Discovery , Humans , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Receptors, Transferrin/genetics , Receptors, Transferrin/metabolism , Ultrasonic Waves , Viruses/geneticsSubject(s)
Birds/physiology , Brain/physiology , Chiroptera/physiology , Language Disorders/genetics , Vocalization, Animal/physiology , Animals , Forkhead Transcription Factors/genetics , Gene Expression , Humans , Mammals/physiology , Membrane Proteins/genetics , Nerve Net/physiology , Nerve Tissue Proteins/geneticsSubject(s)
Aedes/genetics , Insect Proteins/genetics , Olfactory Perception/physiology , Olfactory Receptor Neurons/physiology , Receptors, Odorant/genetics , Smell/physiology , Aedes/drug effects , Aedes/metabolism , Animals , Gene Editing/methods , Gene Expression Regulation , Humans , Insect Proteins/antagonists & inhibitors , Insect Proteins/metabolism , Insect Repellents/chemistry , Insect Repellents/pharmacology , Odorants/analysis , Olfactory Perception/drug effects , Olfactory Receptor Neurons/cytology , Olfactory Receptor Neurons/drug effects , Receptors, Odorant/antagonists & inhibitors , Receptors, Odorant/metabolism , Reverse Genetics/methods , Smell/drug effectsABSTRACT
Dorsal premotor (PMd) and primary motor (M1) cortices play a central role in mapping sensation to movement. Many studies of these areas have focused on correlation-based tuning curves relating neural activity to task or movement parameters, but the link between tuning and movement generation is unclear. We recorded motor preparatory activity from populations of neurons in PMd/M1 as macaque monkeys performed a visually guided reaching task and show that tuning curves for sensory inputs (reach target direction) and motor outputs (initial movement direction) are not typically aligned. We then used a simple, causal model to determine the expected relationship between sensory and motor tuning. The model shows that movement variability is minimized when output neurons (those that directly drive movement) have target and movement tuning that are linearly related across targets and cells. In contrast, for neurons that only affect movement via projections to output neurons, the relationship between target and movement tuning is determined by the pattern of projections to output neurons and may even be uncorrelated, as was observed for the PMd/M1 population as a whole. We therefore determined the relationship between target and movement tuning for subpopulations of cells defined by the temporal duration of their spike waveforms, which may distinguish cell types. We found a strong correlation between target and movement tuning for only a subpopulation of neurons with intermediate spike durations (trough-to-peak â¼350 µs after high-pass filtering), suggesting that these cells have the most direct role in driving motor output.SIGNIFICANCE STATEMENT This study focuses on how macaque premotor and primary motor cortices transform sensory inputs into motor outputs. We develop empirical and theoretical links between causal models of this transformation and more traditional, correlation-based "tuning curve" analyses. Contrary to common assumptions, we show that sensory and motor tuning curves for premovement preparatory activity do not generally align. Using a simple causal model, we show that tuning-curve alignment is only expected for output neurons that drive movement. Finally, we identify a physiologically defined subpopulation of neurons with strong tuning-curve alignment, suggesting that it contains a high concentration of output cells. This study demonstrates how analysis of movement variability, combined with simple causal models, can uncover the circuit structure of sensorimotor transformations.
Subject(s)
Feedback, Sensory/physiology , Models, Neurological , Motor Cortex/physiology , Nerve Net/physiology , Psychomotor Performance/physiology , Visual Perception/physiology , Animals , Computer Simulation , Macaca , MaleABSTRACT
Even well practiced movements cannot be repeated without variability. This variability is thought to reflect "noise" in movement preparation or execution. However, we show that, for both professional baseball pitchers and macaque monkeys making reaching movements, motor variability can be decomposed into two statistical components, a slowly drifting mean and fast trial-by-trial fluctuations about the mean. The preparatory activity of dorsal premotor cortex/primary motor cortex neurons in monkey exhibits similar statistics. Although the neural and behavioral drifts appear to be correlated, neural activity does not account for trial-by-trial fluctuations in movement, which must arise elsewhere, likely downstream. The statistics of this drift are well modeled by a double-exponential autocorrelation function, with time constants similar across the neural and behavioral drifts in two monkeys, as well as the drifts observed in baseball pitching. These time constants can be explained by an error-corrective learning processes and agree with learning rates measured directly in previous experiments. Together, these results suggest that the central contributions to movement variability are not simply trial-by-trial fluctuations but are rather the result of longer-timescale processes that may arise from motor learning.