Representation of moving stimuli by somatosensory neurons.

The findings obtained in neurophysiological and psychophysical investigations using tactile stimuli that move at constant velocity across the skin are reviewed. For certain neurons in the postcentral gyrus of the cerebral cortex (S-I) of macaque monkeys, direction of stimulus motion is a "trigger feature" i.e., moving tactile stimuli evoke vigorous discharge activity in these neurons only if the stimuli are moved in a particular direction across the receptive field. This directional selectivity is maximal when stimulus velocity is between 5 and 50 cm/sec, and falls off rapidly at lower or higher velocities. The capacity for human subjects to correctly identify the direction of stimulus motion on the skin exhibits a similar dependence on stimulus velocity. The similar effects of velocity on neural and psychophysical measures of directional sensitivity support the idea that direction of stimulus motion on the skin can only be recognized if the moving stimulus optimally activates the group of S-I neurons for which that directions of simulus motion is the trigger feature.     

Neuronal activities of the visual field of the cerebral cortex modulated by reserpine-induced PGO waves

The modulatory influence of reserpine-induced PGO wave upon the spontaneous activity of visual cortical neurons was examined in acutely prepared cats. Unitary discharge of cortical neurons was recorded extracellularly with glass micropipettes. Of twenty three neurons three showed a vigorous discharge synchronously with a certain phase of PGO wave. One neuron was strongly suppressed by the occurrence of PGO wave. Three neurons showed an increase and one neuron showed a decrease, respectively, in discharge in a loose correlation with PGO wave. This study has demonstrated the presence of a unique group of neurons which show a burst discharge or a complete silence in a precisely phase-lock manner when reserpine-induced PGO wave occurred.     

Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

A stimulus-dependent connectivity analysis of neuronal networks

We present an analysis of interactions among neurons in stimulus-driven networks that is designed to control for effects from unmeasured neurons. This work builds on previous connectivity analyses that assumed connectivity strength to be constant with respect to the stimulus. Since unmeasured neuron activity can modulate with the stimulus, the effective strength of common input connections from such hidden neurons can also modulate with the stimulus. By explicitly accounting for the resulting stimulus-dependence of effective interactions among measured neurons, we are able to remove ambiguity in the classification of causal interactions that resulted from classification errors in the previous analyses. In this way, we can more reliably distinguish causal connections among measured neurons from common input connections that arise from hidden network nodes. The approach is derived in a general mathematical framework that can be applied to other types of networks. We illustrate the effects of stimulus-dependent connectivity estimates with simulations of neurons responding to a visual stimulus. This research was supported by the National Science Foundation grants DMS-0415409 and DMS-0748417.     

Behavior-related neuronal reactions and dynamics of neuronal activity

Functionally, behavior-related discharges of associative neurons are an efferent flow of pulses continuously generated over the course of each behavioral act of an animal. However, predominant research approaches are based on the "stimulus - reaction" principle. Analysis of the dynamics of unit activity in monkeys during performance of a multi-step behavioral complex showed that differences related to different behavioral acts consist in composition changes in the active neurons (or their recombination) rather than in a number of responsive cells or involvement of action-specific neurons. Each combination of active neurons ensures the distribution of efferent signals characteristic of the given combination. These findings suggest the addressing coding of the efferent neuronal signals.     

Unit responses of the squirrel visual cortex to shaped visual stimuli

Visual cortical unit responses of the squirrelSciurus vulgaris to shaped visual stimuli (stationary and moving spots and bands) were studied. Neurons responding selectively to the direction of stimulus movement and orientation of lines and those not responding selectively to these features were distinguished. Many neurons, whether responding selectively or not to movement direction, were specifically sensitive to high speeds of movement, of the order of hundreds of degrees per second. This selectivity in neurons responding selectively to movement direction persisted at these high speeds, despite the short time taken by the stimulus to move across the receptive field. Neurons responding selectively to line orientation were sensitive to lower speeds of stimulus movement — from units to tens of degrees per second. Neuronal sensitivity to high speeds of stimulus movement is achieved through rapid summation of excitation from large areas of the receptive field crossed by the fast-moving stimulus. Selectivity of the response to movement direction is produced under these conditions with the aid of directed short-latency inhibition, inhibiting unit activity for stimulus movement in "zero" direction.     

Measures of neuronal response based on nonparametric tests

Two response indices characterizing the stimulus effect on spontaneously active neurons are developed. They are based on a non-parametric comparison of interspike interval distributions under the spontaneous and the stimulus condition. The response indices obtained with repeated stimuli can be combined into a single multiple-trial index. The method is tested both with different types of simulated spike activity and with actual single unit activity recorded from an auditory centre of a songbird.Supported by Deutsche Forschungsgemeinschaft within Sonderforschungsbereich 114 (Bionach)     

Testing the efficiency of sensory coding with optimal stimulus ensembles

According to Barlow's seminal "efficient coding hypothesis," the coding strategy of sensory neurons should be matched to the statistics of stimuli that occur in an animal's natural habitat. Using an automatic search technique, we here test this hypothesis and identify stimulus ensembles that sensory neurons are optimized for. Focusing on grasshopper auditory receptor neurons, we find that their optimal stimulus ensembles differ from the natural environment, but largely overlap with a behaviorally important sub-ensemble of the natural sounds. This indicates that the receptors are optimized for peak rather than average performance. More generally, our results suggest that the coding strategies of sensory neurons are heavily influenced by differences in behavioral relevance among natural stimuli.     

A possible mechanism of participation of dopaminergic cells and striatal cholinergic interneurons in the conditioned selection of motor activity

A possible mechanism of participation of cholinergic striatal interneurons and dopaminergic cells in conditioned selection of a certain types of motor activity is proposed. This selection is triggered by simultaneous increase in the activity of dopaminergic cells and a pause in the activity of cholinergic interneurons in response to a conditioned stimulus. This pause is promoted by activation of striatal inhibitory interneurons and action of dopamine at D2 receptors on cholinergic cells. Opposite changes in dopamine and acetylcholine concentration synergistically modulate the efficacy of corticostriatal inputs, modulation rules for the "strong" and "weak" corticostriatal inputs are opposite. Subsequent reorganization of neuronal firing in the loop cortex--basal ganglia--thalamus--cortex results in amplification of activity of the group of cortical neurons that strongly activate striatal cells, and simultaneous suppression of activity of another group of cortical neurons that weakly activate striatal cells. These changes can underlie a conditioned selection of motor activity performed with involvement of the motor cortex. As follows from the proposed model, if the time delay between conditioned and unconditioned stimuli does not exceed the latency of responses of dopaminergic and cholinergic cells (about 100 ms), conditioned selection of motor activity and learning is problematic.     

Frequency-dependent response of SI RA-class neurons to vibrotactile stimulation of the receptive field

Three types of experiment were carried out on anesthetized monkeys and cats. In the first, spike discharge activity of rapidly adapting (RA) SI neurons was recorded extracellularly during the application of different frequencies of vibrotactile stimulation to the receptive field (RF). The second used the same stimulus conditions to study the response of RA-I (RA) cutaneous mechanoreceptive afferents. The third used optical intrinsic signal (OIS) imaging and extracellular neurophysiological recording methods together, in the same sessions, to evaluate the relationship between the SI optical and RA neuron spike train responses to low- vs high-frequency stimulation of the same skin site. RA afferent entrainment was high at all frequencies of stimulation. In contrast, SI RA neuron entrainment was much lower on average, and was strongly frequency-dependent, declining in near-linear fashion from 6 to 200 Hz. Even at 200 Hz, however, unambiguous frequencyfollowing responses were present in the spike train activity of some SI RA neurons. These entrainment results support the "periodicity hypothesis" of Mountcastle et al. ( J Neurophysiol 32: 452-484, 1969) that the capacity to discriminate stimulus frequency over the range 5-50 Hz is attributable to the ability of SI RA pyramidal neurons to discharge action potentials in consistent temporal relationship to stimulus motion, and raise the possibility that perceptual frequency discriminative capacity at frequencies between 50 and 200 Hz might be accounted for in the same way. An increase in vibrotactile stimulus frequency within the range 6-200 Hz consistently resulted in an increase in RA afferent mean spike firing rate (M FR). SI RA neuron M FR also increased as frequency increased between 6 and 50 Hz, but declined as stimulus frequency was increased over the range 50-200 Hz. At stimulus frequencies > 100 Hz, and at positions in the RF other than the receptive field center (RF center ), SI RA neuron MFR declined sharply within 0.5-2s of stimulus onset and rebounded transiently upon stimulus termination. In contrast, when the stimulus was applied to the RF center, MFR increased with increasing frequency and tended to remain well maintained throughout the period of high-frequency stimulation. The evidence obtained in "combined" OIS imaging and extracellular microelectrode recording experiments suggests that SI RA neurons with an RF center that corresponds to the stimulated skin site occupy small foci within the much larger SI region activated by same-site cutaneous flutter stimulation, while for the RA neurons located elsewhere in the large SI region activated by a flutter stimulus, the stimulus site and RF center are different.     

One picture is worth at least a million neurons

How many neurons participate in the representation of a single visual image? Answering this question is critical for constraining biologically inspired models of object recognition, which vary greatly in their assumptions from few "grandmother cells" to numerous neurons in widely distributed networks. Functional imaging techniques, such as fMRI, provide an opportunity to explore this issue, since they allow the simultaneous detection of the entire neuronal population responding to each stimulus. Several studies have shown that fMRI BOLD signal is approximately proportional to neuronal activity. However, since it provides an indirect measure of this activity, obtaining a realistic estimate of the number of activated neurons requires several intervening steps. Here, we used the extensive knowledge of primate V1 to yield a conservative estimate of the ratio between hemodynamic response and neuronal firing. This ratio was then used, in addition to several cautious assumptions, to assess the number of neurons responding to a single-object image in the entire visual cortex and particularly in object-related areas. Our results show that at least a million neurons in object-related cortex and about two hundred million neurons in the entire visual cortex are involved in the representation of a single-object image.     

Neural coding of gustatory information.

The nervous system encodes information relating chemical stimuli to taste perception, beginning with transduction mechanisms at the receptor and ending in the representation of stimulus attributes by the activity of neurons in the brain. Recent studies have rekindled the long-standing debate about whether taste information is coded by the pattern of activity across afferent neurons or by specifically tuned 'labeled lines'. Taste neurons are broadly tuned to stimuli representing different qualities and are also responsive to stimulus intensity and often to touch and temperature. Their responsiveness is also modulated by a number of physiological factors. In addition to representing stimulus quality and intensity, activity in taste neurons must code information about the hedonic value of gustatory stimuli. These considerations suggest that individual gustatory neurons contribute to the coding of more than one stimulus parameter, making the response of any one cell meaningful only in the context of the activity of its neighbors.     

Associative fear learning enhances sparse network coding in primary sensory cortex

Several models of associative learning predict that stimulus processing changes during association formation. How associative learning reconfigures neural circuits in primary sensory cortex to "learn" associative attributes of a stimulus remains unknown. Using 2-photon in vivo calcium imaging to measure responses of networks of neurons in primary somatosensory cortex, we discovered that associative fear learning, in which whisker stimulation is paired with foot shock, enhances sparse population coding and robustness of the conditional stimulus, yet decreases total network activity. Fewer cortical neurons responded to stimulation of the trained whisker than in controls, yet their response strength was enhanced. These responses were not observed in mice exposed to a nonassociative learning procedure. Our results define how the cortical representation of a sensory stimulus is shaped by associative fear learning. These changes are proposed to enhance efficient sensory processing after associative learning.     

Responses of medullary neurons to microstimulation of the "locomotor strip" in cats

Synaptic responses of medullary neurons to stimulation of the bulbar locomotor strip with a current of about 20 µA were studied by an extracellular recording method in mesencephalic cerebellectomized cats. The mean latent period of response of 177 neurons was 3.2 msec. Neurons in which synaptic responses appeared were located in both the lateral and the medial parts of the reticular formation, but short-latency responses were recorded predominantly in the lateral part. In response to a single stimulus 32% of neurons generated a discharge of 2–4 spikes. "Respiratory" neurons were not excited by stimulation of the locomotor point. The results indicate that neurons of the locomotor strip may have an excitatory action not only on each other, but also on neurons located medially. The possible mechanisms of the spread of activity to the superior cervical segments of the spinal cord are discussed.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 3, pp. 275–282, May–June, 1981.     

Respiratory rhythmicity in the cat.

Brain stem respiratory neuron activity in the cat was studied in relation to efferent outflow (phrenic discharge) under the influence of several forcing inputs: 1) CO2 tension: hypocapnia produces disappearance of firing in some neurons, and conversion of respiratory-modulated to continuous (tonic) firing in others. 2) Lung inflation: during the Bruer-Hering reflex, some neurons have "classical" responses and others have "paradoxical" responses (i.e., opposite in direction to peripheral discharge). 3) Electrical stimulation: stimulus trains to the pneumotaxic center region (rostral lateral pons) produce phase-switching, whose threshold is: a) sharp (indicating action of positive-feedback mechanisms), and b) dependent on timing of stimulus delivery (indicating continuous excitability changes during each respiratory phase). Auto- and crosscorrelation analysis revealed the existence of short-term interactions between: a) medullary inspiratory (I) neurons and phrenic motoneurons; b) pairs of medullary I neurons; c) medullary I neurons and expiratory (E) neurons. A model of the respiratory oscillator is presented, in which the processes of conversion of tonic to phasic activity and switching of the respiratory phases are explained by recurrent excitatory and inhibitory loops.     

Interacting roles of attention and visual salience in V4

Attention increases the contrast gain of V4 neurons, causing them to respond to an attended stimulus as though its contrast had increased. When multiple stimuli appear within a neuron's receptive field (RF), the neuron responds primarily to the attended stimulus. This suggests that cortical cells may be "hard wired" to respond preferentially to the highest-contrast stimulus in their RF, and neural systems for attention capitalize on this mechanism by dynamically increasing the effective contrast of the stimulus that is task relevant. To test this, we varied the relative contrast of two stimuli within the recorded neurons' RFs, while the monkeys attended away to another location. Increasing the physical contrast of one stimulus caused V4 neurons to respond preferentially to that stimulus and reduced their responses to competing stimuli. When attention was directed to the lower-contrast stimulus, it partially overcame the influence of a competing, higher-contrast stimulus.     

Voltage-dependent burst-to-tonic switching of thalamic cell activity: an in vitro study

The electroresponsiveness of mammalian thalamic neurons was studied in a slice preparation of the guinea pig diencephalon. Although the morphology of the cells varied, their electroresponsive properties were the same. Stimulation of thalamic cells at a membrane potential more negative than--60 mV produced burst responses and stimulation of more depolarized levels produced tonic firing of fast spikes. The burst response is generated by an inactivating Ca++-conductance. It is seen as a slow Ca++-spike which in turn triggers fast Na+-spikes. The Ca++-conductance is deinactivated by hyperpolarization beyond--60 mV. The membranes of thalamic neurons contain a number of other conductances including a Ca++-dependent K+-conductance producing spike afterhyperpolarization and a non-inactivating Na+-conductance which plays an important role during tonic activity of the cells. The early part of a response to a long-lasting stimulus given at rest or at a hyperpolarized level is dominated by the burst and thus is is independent of the stimulus amplitude. During the late part of such a response the firing rate is highly dependent of the stimulus intensity. Current-frequency plots for the first inter-spike intervals after the burst during long stimuli are upward convex, but after "steady-state" is reached the plots are almost linear.     

Representation of binary pheromone blends by glomerulus-specific olfactory projection neurons

An outstanding challenge in olfactory neurobiology is to explain how glomerular networks encode information about stimulus mixtures, which are typical of natural olfactory stimuli. In the moth Manduca sexta, a species-specific blend of two sex-pheromone components is required for reproductive signaling. Each component stimulates a different population of olfactory receptor cells that in turn target two identified glomeruli in the macroglomerular complex of the males antennal lobe. Using intracellular recording and staining, we examined how responses of projection neurons innervating these glomeruli are modulated by changes in the level and ratio of the two essential components in stimulus blends. Compared to projection neurons specific for one component, projection neurons that integrated information about the blend (received excitatory input from one component and inhibitory input from the other) showed enhanced ability to track a train of stimulus pulses. The precision of stimulus-pulse tracking was furthermore optimized at a synthetic blend ratio that mimics the physiological response to an extract of the females pheromone gland. Optimal responsiveness of a projection neuron to repetitive stimulus pulses therefore appears to depend not only on stimulus intensity but also on the relative strength of the two opposing synaptic inputs that are integrated by macroglomerular complex projection neurons.     

Selectivity of visual cortical neurons of rabbits to magnitude of moving stimuli

Unit responses of the rabbit visual cortex were investigated in relation to size of visual stimuli moving in their receptive field. With an increase in size of the stimulus in a direction perpendicular to the direction of movement ("width" of the stimulus) an initial increase in the intensity of the unit response through spatial summation of excitory effects is followed by a decrease through lateral inhibition. This inhibition is observed between zones of the receptive field which behave as activating when tested by a stimulus of small size. Each neuron has its own "preferred" size of stimuli evoking its maximal activation. No direct correlation is found between the "preferred" stimulus size and the size of the receptive field. With a change in stimulus size in the direction of movement ("length" of the stimulus) the responses to stimuli of optimal size may be potentiated through mutual facilitation of the effects evoked by the leading and trailing edges of the stimulus and weakened in response to stimuli of large size. The selective behavior of the neurons with respect to stimulus size is intensified in the case of coordinated changes in their length and width. It is postulated that the series of neurons responding to stimuli of different "preferred" dimensions may constitute a system classifying stimuli by their size.A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 6, pp. 636–644, November–December, 1972.     

Central processing of sensory information in electric fish

Summary Comparative studies of neural mechanisms underlying the perception of natural stimulus patterns and the control of adaptive behavioral responses have revealed organizational principles that are shared by a wide spectrum of animals. Mechanisms of perception and motor control are commonly executed in a distributed network of neurons that lack pontifical elements. Individual neurons even at an organizational level as high as the optic tectum may still have very general response characteristics, and the recruitment of individual neurons reveals little about the nature of the stimulus situation outside. Only the joint evaluation of messages from large populations of such neurons yields unambiguous pictures of the outside world. Stimulus variables are commonly mapped continuously within a stratum of neurons so that their variation over time can be monitored by mechanisms similar to motion detection in a retina. The ordered representation of a stimulus variable within an array of broadly tuned elements allows for a degree of stimulus resolution that by far exceeds that of individual elements in the array. Neural systems are burdened by their evolutionary history and suffer from imperfections that are overcome by a patchwork of compensations. The existence of multiple neuronal representations of sensory information and multiple circuits for the control of behavioral responses should provide the necessary freedom for evolutionary tinkering and the invention of new designs.