Erik P. Cook

Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons

Most neurons receive thousands of synaptic inputs onto widely spread dendrites. Because of dendritic filtering, distant synapses should have less efficacy than proximal ones. To investigate this, we characterized the amplitude and kinetics of excitatory synaptic input across the apical dendrites of CA1 pyramidal neurons using dual whole-cell recordings. We found that dendritic EPSP amplitude increases with distance from the soma, counterbalancing the filtering effects of the dendrites and reducing the location dependence of somatic EPSP amplitude. Dendritic current injections and a multi-compartmental computer model demonstrated that dendritic membrane properties have only a minor role in elevating the local EPSP. Instead a progressive increase in synaptic conductance seems to be primarily responsible for normalizing the amplitudes of individual inputs.

Dynamics of neuronal responses in macaque MT and VIP during motion detection.

We examined how the relationship between neuronal activity and behavior evolved over time during a motion-detection task. Recording from two regions of visual cortex that process motion, the middle temporal (MT) and ventral intraparietal (VIP) areas, we used the time it took subjects to detect a motion stimulus to evaluate the dynamics of the underlying neuronal signals. Single-neuron activity was correlated with stimulus detection and reaction time (RT) in both areas. The rising edge of the population response from both areas was highly predictive of RT using a simple threshold-detection model. The time course of the population responses, however, differed between MT and VIP. For MT, the onset of the neuronal response was relatively constant, whereas for VIP the onset of the neuronal responses increased with RT. In contrast to previous studies, we found that single neurons were not reliable detectors of the motion signal when constrained by realistic detection times.

Attentional Modulation of Motion Integration of Individual Neurons in the Middle Temporal Visual Area

We examined how spatially directed attention affected the integration of motion in neurons of the middle temporal (MT) area of visual cortex. We recorded from single MT neurons while monkeys performed a motion detection task under two attentional states. Using 0% coherent random dot motion, we estimated the optimal linear transfer function (or kernel) between the global motion and the neuronal response. This linear kernel filtered the random dot motion across direction, speed, and time. Slightly less than one-half of the neurons produced reasonably well defined kernels that also tended to account for both the directional selectivity and responses to coherent motion of different strengths. This subpopulation of cells had faster, more transient, and more robust responses to visual stimuli than neurons with kernels that did not contain well defined regions of integration. For those neurons that had large attentional modulation and produced well defined kernels, we found attention scaled the temporal profile of the transfer function with no appreciable shift in time or change in shape. Thus, for MT neurons described by a linear transfer function, attention produced a multiplicative scaling of the temporal integration window.

The Effect of Microsaccades on the Correlation between Neural Activity and Behavior in Middle Temporal, Ventral Intraparietal, and Lateral Intraparietal Areas

It is widely reported that the activity of single neurons in visual cortex is correlated with the perceptual decision of the subject. The strength of this correlation has implications for the neuronal populations generating the percepts. Here we asked whether microsaccades, which are small, involuntary eye movements, contribute to the correlation between neural activity and behavior. We analyzed data from three different visual detection experiments, with neural recordings from the middle temporal (MT), lateral intraparietal (LIP), and ventral intraparietal (VIP) areas. All three experiments used random dot motion stimuli, with the animals required to detect a transient or sustained change in the speed or strength of motion. We found that microsaccades suppressed neural activity and inhibited detection of the motion stimulus, contributing to the correlation between neural activity and detection behavior. Microsaccades accounted for as much as 19% of the correlation for area MT, 21% for area LIP, and 17% for VIP. While microsaccades only explain part of the correlation between neural activity and behavior, their effect has implications when considering the neuronal populations underlying perceptual decisions.

The Functional Link between Area MT Neural Fluctuations and Detection of a Brief Motion Stimulus

Fluctuations of neural firing rates in visual cortex are known to be correlated with variations in perceptual performance. It is important to know whether these fluctuations are functionally linked to perception in a causal manner or instead reflect non-causal processes that arise after the perceptual decision is made. We recorded from middle temporal (MT) neurons from monkey subjects while they detected the random occurrence of a brief 50 ms motion pulse that occurred in either of two (or simultaneously in both) random dot patches located in the same hemisphere. The receptive field parameters of the motion pulse were matched to that preferred by each MT neuron under study. This task contained uncertainty in both space and time because, on any given trial, the subjects did not know which patch would contain the motion pulse or when the motion pulse would occur. Covariations between MT activity and behavior began just before the motion pulse onset and peaked at the maximum neural response. These neural–behavioral covariations were strongest when only one patch contained the motion pulse and were still weakly present when a patch did not contain a motion pulse. A feedforward temporal integration model with two independent detector channels captured both the detection performance and evolution of the neural–behavior covariations over time and stimulus condition. The results suggest that, when detecting a brief visual stimulus, there is a causal relationship between fluctuations in neural activity and variations in behavior across trials.

The Effect of Middle Temporal Spike Phase on Sensory Encoding and Correlates with Behavior during a Motion-Detection Task

Previous studies have shown that sensory neurons that are the most informative of the stimulus tend to be the best correlated with the subjects perceptual decision. We wanted to know whether this relationship might also apply to short time segments of a neurons response. We asked whether spikes that conveyed more information about a motion stimulus were also more tightly linked to the perceptual behavior. We examined single-neuron activity in middle temporal (MT) area while monkeys performed a motion-detection task. Because of a slow stimulus update (every 27 ms), activity in many MT neurons was entrained and phase-locked to the stimulus. These stimulus-entrained neuronal oscillations allowed us to separate spikes based on phase. We observed a large amount of variability in how spikes at different phases of the oscillation encoded the stimulus, as revealed by the spike-triggered average of the motion. Spikes during certain phases of the cycle were much more informative about the presence of coherent motion than others. Importantly, we found that the phases that were the most informative about the motion stimulus were also more correlated with the behavioral performance and reaction time of the animal. Our results suggest that the relationship between a neurons spikes, the stimulus, and behavior can vary on a time scale of tens of milliseconds.

Behavioral Time Course of Microstimulation in Cortical Area MT

Electrical stimulation of the brain is a valuable research tool and has shown therapeutic promise in the development of new sensory neural prosthetics. Despite its widespread use, we still do not fully understand how current passed through a microelectrode interacts with functioning neural circuits. Past behavioral studies have suggested that weak electrical stimulation (referred to as microstimulation) of sensory areas of cortex produces percepts that are similar to those generated by normal sensory stimuli. In contrast, electrophysiological studies using in vitro or anesthetized preparations have shown that neural activity produced by brief microstimulation is radically different and longer lasting than normal responses. To help reconcile these two aspects of microstimulation, we examined the temporal properties that microstimulation has on visual perception. We found that brief application of subthreshold microstimulation in the middle temporal (MT) area of visual cortex produced smaller and longer-lasting effects on motion perception compared with an equivalent visual stimulus. In agreement with past electrophysiological studies, a computer simulation reproduced our behavioral effects when the time course of a single microstimulation pulse was modeled with three components: an immediate fast strong excitatory component, followed by a weaker inhibitory component, and then followed by a long duration weak excitatory component. Overall, these results suggest the behavioral effects of microstimulation in our experiments were caused by the unique and long-lasting temporal effects microstimulation has on functioning cortical circuits.