Conditioned reflex: detector and command neuron

Conditioned reflex is characterized by plasticity resulting in a bilateral selective input-output linking. In simple nervous systems, input stimuli are represented by selective detectors connected with command neurons through plastic synapses strengthened during associative learning and weakened during extinction. The process of associative learning is due to temporal coincidence of excitation in both detector and command neurons. Short-term memory within a plastic synapses is mediated by phosphorilation of postsynaptic receptor molecules not requiring protein synthesis. Long-term synaptic memory parallels expression of immediate early genes that mediates structural gene expression and protein synthesis. A simple detector-command neuron association becomes more complex in the course of evolution. Input mechanism is supplemented with predetector interneurons preceding detectors. Detector selectively tuned to specific input stimulus is converging on a command neuron constitute selectivity mechanism for conditioned reflexes to complex stimuli. The complication also concerns the output mechanisms. Command neurons become more specialized, and an additional link of premotor interneurons is incorporated between command neurons and motor neurons. Via synapses, the command neurons can produce excitation in a particular set of premotor neurons controlling a specific set of motor neurons responsible for behavioral act configuration. Specialization of command neurons in combination with premotor neuron structures increases the variability of outputs. Conditioned reflexes with more complex inputs and more flexible outputs determine the diversity of acquired behaviors.     

Orienting reflex: "targeting reaction" and "searchlight of attention"

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.     

Acquisition of conditioned facial reflexes in the cat: cortical control of different facial movements

The motor cortex plays a role in determining which of three different facial movements is acquired in Pavlovian conditioning experiments. Three separate facial reflexes can be distinguished by recording electromyographic activity from the orbicularis oculi (eye blink) and levator orii (nose twitch) muscles. One in a pure eye blink; a second is a nose twitch; the third is a compound eye blink and nose twitch. Which of these movements is elicited by a click (conditioned stimulus) following associative conditioning is reflected by the pattern of unit activity elicited by the click at the motor cortex. Activity is enhanced, after conditioning, in those units that project polysynaptically to the specific muscles performing the learned movement. This enhancement of activity is, in turn, relatable to an enhanced electrical excitability of the involved neurons. Analogous changes in the excitability of neurons of the motor cortex to applied currents can be produced by local application of cholinergic agents. Iontophoresis of acetylcholine, aceclidine (a cholinomimetic drug), or intracellularly applied cyclic GMP produces changes in single neuron membrane resistance that increase neuronal excitability. The units of the motor cortex that respond preferentially to these agents and to the click conditioned stimuli with short latencies have been identified as pyramidal cells of layer V. The axons of these neurons form the pyramidal tract, a pathway characterized as serving voluntary movement. It appears that this system supports rapid transmission and processing of auditory-motor information used to perform learned movements adaptively, selectively, and discriminatively.     

Neurophysiological changes and dynamics of bound calcium during the development of associative learning in Helix lucorum

Neurophysiological effects and the dynamics of the content of bound calcium (Ca-b) in command neurons (LP1 and RP1) of defensive behavior during food aversion conditioning are studied inHelix lucorum. In the case of associative learning, there arises in these cells both a response to the conditioned stimulus and a nonspecific facilitation of the reactions to sensory stimuli that is characteristic for the state of sensitization. A response to the presentation of a conditioned stimulus is detected approximately 30 min after the development of long-term sensitization. The use of three or more paired stimuli reveals the characteristic dynamics of the level of Ca-b, which correlates with the neurophysiological effects and differs from the changes in Ca-b content during the development of "pure" sensitization. It is thought that the command neuron of defense behavior exhibits inHelix differences of the molecular-cellular mechanisms lying at the basis of the development of associative learning and sensitization.P. K. Anokhin Institute of Normal Physiology, Russian Academy of Sciences, Moscow. I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg. Translated from Neirofiziologiya, Vol. 24, No. 6, pp. 691–701, November–December, 1992.     

Cellular mechanisms of behavioural plasticity in simple nervous systems

In the present study, we will try to single out several principles of the nervous system functioning essential for describing the mechanisms of learning and memory, basing on our own experimental investigation of cellular mechanisms of memory in the nervous system of gastropod molluscs and literature data as follows: (1) Main changes in functioning due to learning occur in the interneurons; (2) Due to learning some synaptic inputs of command neurons selectively change its effectivity; (3) Reinforcement is not related to activity of the neural chain receptor-sensory neuron-interneuron-motoneuron-effector; reinforcement is mediated via activity of modulatory neurons, and in some cases can be exerted by a single neuron; (4) Activity of modulatory neurons is necessary for development of plastic modifications of behaviour (including associative), but is not needed for recall of conditioned responses. At the same time, the modulatory neurons (in fact they constitute a neural reinforcement system) are necessary for recall of context associative memory; (5) Changes due to learning occur at least in two independent loci in the nervous system.     

Coding of stimulus movement parameters in cat visual system

The principal component analysis of matrices composed of spike numbers generated by visual neurons of cats in response to motion of simple and complex stimuli revealed vector encoding. Responses of detectors of moving dot direction and detectors of oblique line orientation are encoded independently in V1 and V2 cortices by excitation of two cardinal neurons. Each pair of these neurons generates sine and cosine functions. Responses of detectors in the association cortex selective to specific orientation of moving stripes depend on the activity of four cardinal neurons which sum up the excitation incoming from the direction and orientation channels.     

A persistent cellular change in a single modulatory neuron contributes to associative long-term memory

Most neuronal models of learning assume that changes in synaptic strength are the main mechanism underlying long-term memory (LTM) formation. However, we show here that a persistent depolarization of membrane potential, a type of cellular change that increases neuronal responsiveness, contributes significantly to a long-lasting associative memory trace. The use of a model invertebrate network with identified neurons and known synaptic connectivity had the advantage that the contribution of this cellular change to memory could be evaluated in a neuron with a known function in the learning circuit. Specifically, we used the well-understood motor circuit underlying molluscan feeding and showed that a key modulatory neuron involved in the initiation of feeding ingestive movements underwent a long-term depolarization following behavioral associative conditioning. This depolarization led to an enhanced single cell and network responsiveness to a previously neutral tactile conditioned stimulus, and the persistence of both matched the time course of behavioral associative memory. The change in the membrane potential of a key modulatory neuron is both sufficient and necessary to initiate a conditioned response in a reduced preparation and underscores its importance for associative LTM.     

Computation of responses to color and brightness differences of neurons in the rabbit lateral geniculate nucleus

Changes in activity of 51 neurons in the rabbit lateral geniculate nucleus evoked by the replacement of eight color and eight achromatic stimuli in pairs were analyzed. It was found that neurons displayed the earliest phasic (within 50-90 ms after the replacement) and tonic response components. The earliest component strongly correlated with differences between stimuli, whereas the tonic component depended on stimuli intensity. Analysis of phasic component revealed two neuronal populations: the first group of cells was specialized for stimuli differentiation only by their intensities, and, and the second group could measure differences in colors and intensities. Neuronal perceptual spaces were reconstructed using the average of the earliest response component as a measure of differences between stimuli. Spaces of 44 neurons (86%) were two-dimensional with brightness and darkness axes. Such neurons had the same structures of space for color and achromatic stimuli. Spaces of 7 neurons (14%) were four-dimensional with two chromatic and two achromatic axes. The structures of perceptual space reconstructed from neurons in the lateral geniculate nucleus were identical to the spaces calculated from the neurons in the primary visual cortex. The structure of the perceptual space reconstructed from neuronal spikes was also similar to space calculated from the N85 visual evoked potential component recorded under similar conditions and to another space reconstructed on the basis of rabbit's instrumental learning. This fact confirmed the general principle of vector coding in the visual system. The tonic component of the most of neurons in the lateral geniculate nucleus showed a linear correlation with changes in intensities, thereby these neurons could be characterized as pre-detectors for cortical selective detectors.     

Elementary and compound postsynaptic potentials in the defensive command neurons of Helix lucorum

The present communication concerns with the analysis of elementary and the compound excitatory postsynaptic potentials (eEPSPs and cEPSPs) recorded by intracellular microelectrode from an identified defensive command neuron of the snail Helix lucorum. The eEPSPs were evoked by single presynaptic action potentials (APs) elicited by cationic current injection into one of the identified sensory neurons synapsing on the respective command neuron. The cEPSPs were elicited by local brief tactile stimuli on the skin or internal organs. It was shown that the cEPSPs amplitudes depend mainly on the number of activated sensory neurons. Compound EPSPs depend also on frequency and the number of APs in the bursts occurring in a single neuron. Presynaptic APs having frequency 2-10 Hz evoke high frequency depression of that eEPSPs after an interval is followed by post-tetanic potentiation of single eEPSPs. Preceding stimulation of a pneumostom area facilitates the cEPSPs elicited by repeated stimulation of viscera. The eEPSPs from the same visceral area demonstrate no heterosynaptic facilitation in experiments with double parallel intracellular recording from responsive sensory and command neurons. The different types of the eEPSPs plasticity are discussed according to their contribution cEPSPs plastic changes.     

A descending contralateral directionally selective movement detector in the praying mantis <Emphasis Type="Italic">Tenodera aridifolia</Emphasis>

Extracellular recordings were made from a directionally selective neuron in the ventral nerve cord of mantises. The neuron’s preferred direction of motion was forward and upward over the compound eye contralateral to its axon at the cervical connective. The neuron was sensitive to wide-field motion stimuli, resistant to habituation, and showed transient excitation in response to light ON and OFF stimuli. Its responses to drifting gratings depended on the temporal frequency and contrast of the stimulus. These results suggest that the neuron receives input from correlation-type motion detectors.     

Visual associative memory and the orientation-contingent color after-effect

The traditional explanation of the McCollough effect (ME) by selective adaptation of single detectors selective to color and orientation suffers from a number of inconsistencies: 1) the ME lasts much longer (from several days up to 3 months) than the ordinary adaptation, the decay of the effect being completely arrested by night sleep or occluding the eye for a long time; 2) the strength of the ME practically does not depend on the intensity of adapting light; and 3) a set of related pattern-contingent after-effects discovered later required for such an explanation new detectors, specific for other patterns. These properties can be explained, however, in the framework of associative memory and novelty filters. A computational model has been developed, which consists of 1) an input layer of two (left and right eyes) square matrices with two analog receptors (red and green) in each pixel, 2) an isomorphic associative neural layer, each analog neuron being synaptically connected with all receptors of both eyes, and 3) an output layer (novelty filter). The modification of synaptic efficacies conforms to the Hebb learning rule. The function of the model was examined by simulation. After a few presentations of colored gratings, the model displays the ME that is slowly destroyed by subsequent presentations of random pictures. With a sufficiently large receptor matrix, the effect lasts a thousand times longer than the period of adaptation. Continuous darkness does not change the strength of the effect. Like in real ME, the model does not display interocular transfer. The model can account for different pattern-contingent color after-effects without assuming any predetermined specific detectors. Such detectors are constructed in the course of adaptation to specific stimuli (gratings).     

Searching for optimal stimuli: ascending a neuron’s response function

Many methods used to analyze neuronal response assume that neuronal activity has a fundamentally linear relationship to the stimulus. However, some neurons are strongly sensitive to multiple directions in stimulus space and have a highly nonlinear response. It can be difficult to find optimal stimuli for these neurons. We demonstrate how successive linear approximations of neuronal response can effectively carry out gradient ascent and move through stimulus space towards local maxima of the response. We demonstrate search results for a simple model neuron and two models of a highly selective neuron.     

Responses of Neurons of the Extrastriate Area 21b of the Cat Brain Cortex to Changes in Orientation of Moving Visual Stimuli

We studied the responses of neurons of the extrastriate cortical area 21b of the cat to changes in orientation of the movements of visual stimuli within the receptive field (RF) of the neuron under study. Our experiments demonstrated that 24 of 108 cells (22%) responded differentially to a certain extent to orientation of the movements of visual stimuli. As a whole, neurons of the area 21b did not demonstrate fine tuning on the optimum angle of orientation. In many cases, neuronal responses to different orientations of the movement of visual stimulus depended significantly on specific parameters of this stimulus (its shape, dimensions, and contrast). Some directionally sensitive neurons responded to a change in orientation of the movement of visual stimuli by modification of the index of directionality. We also studied spatial organization of the RF of neurons with the presentation of stationary visual stimuli. Comparison of the neuronal responses to a change in orientation of the movements of stimuli and to presentation of stationary stimuli showed that the correlation between the orientation sensitivity of the neuron under study and the stationary functional organization of its RF was insignificant. We hypothesize that inhibitory processes and subthreshold influences from a space surrounding the RF play a special role in the formation of the neuronal responses generated in the associative visual cortical regions to visual stimulation.     

Principle of neuronal organization of defensive reflexes in mollusks

Spontaneous and evoked synaptic activity of command neurons for the defensive response of spiracle closing were studied by simultaneous intracellular recording of activity of several identified CNS neurons in snails. Comparison of monosynaptic EPSPs in command neurons evoked by discharges of presynaptic neurons with spontaneous synaptic potentials indicated that the central organization of the defensive reflex is in the form of a two-layered neuron net in which each neuron of the afferent layer possesses a local receptive field, but which overlaps with other afferent neurons. Each neuron of the afferent layer is connected with each neuron of the efferent layer by monosynaptic excitatory connections that differ in efficiency (maximal only with one neuron of the efferent layer). Both receptive fields of neurons of the afferent layer and "fields of efficiency of synaptic connections" are distributed according to the normal law. As a result of this organization the neuron net acquires a new quality: The action of different stimuli leads to the appearance of differently located "spatial excitation profiles" of efferent layer neurons even when this action of the stimulus occurs not at the center of the receptive field.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 26–34, January-February, 1984.     

Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex

The ability to distinguish novel from familiar stimuli allows nervous systems to rapidly encode significant events following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories. During a learning task, we recorded from individual MTL neurons in vivo using microwire electrodes implanted in human epilepsy surgery patients. We report here the discovery of two classes of neurons in the hippocampus and amygdala that exhibit single-trial learning: novelty and familiarity detectors, which show a selective increase in firing for new and old stimuli, respectively. The neurons retain memory for the stimulus for 24 hr. Thus, neurons in the MTL contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning.     

Computation of color and brightness differences by neurons in the rabbit visual cortex

Changes in activity of 54 neurons in the rabbit visual cortex evoked by the replacement of eight color and eight achromatic stimuli in pairs were analyzed. The diffused stimuli generated by color SVGA monitor were used in the experiments. The earliest response of phasic neurons (50-90 ms after the replacement) was strongly correlated with differences between stimuli in color or intensity. This response ("the signal of differences") was used as a basis of a matrix (8 x 8) constructed for each neuron. Such matrices included mean numbers of spikes per second in responses to changes of different stimuli pairs. All matrices were subjected to factor analysis, and the basic axes (the main factors) of sensory spaces were revealed. It was found that 16 neurons (30%) detected only achromatic differences between stimuli. Perceptual spaces of these neurons were two-dimensional with brightness and darkness orthogonal axes. The spaces of 12 neurons (22%) were four-dimensional with two chromatic and two achromatic axes. The structure of the perceptual space reconstructed from neuronal spikes was similar to the space calculated from the early VEP components recorded under similar conditions and to another space reconstructed on the basis of rabbit's instrumental learning. The fundamental coincidence of color spaces revealed by different methods may reflect the general principle of vector coding in the visual system and suggests the coexistence of two independent cortical mechanisms of the detection of chromatic and achromatic differences.     

Network, cellular and molecular mechanisms of plasticity in simple nervous systems

In the present study we will try to single out several principles of the nervous system functioning essential for describing mechanisms of learning and memory basing on our own experimental investigation of cellular mechanisms of memory in the nervous system of gastropod molluscs and literature data: main changes in functioning due to learning occur in effectivity of synaptic inputs and in the intrinsic properties of postsynaptic neurons; due to learning some synaptic inputs of neurons selectively change its effectivity due to pre- and postsynaptic changes, but the induction of plasticity always starts in postsynapse, maintaining of long-term memory in postsynapse is also shown; reinforcement is not related to activity of the neural chain receptor-sensory neuron-interneuron-motoneuron-effector; reinforcement is mediated via activity of modulatory neurons, and in some cases can be exerted by a single neuron; activity of modulatory neurons is necessary for development of plastic modifications of behavior (including associative), but is not needed for recall of conditioned responses. At the same time, the modulatory neurons (in fact they constitute a neural reinforcement system) are necessary for recall of context associative memory; changes due to learning occur at least in two independent loci in the nervous system. A possibility for erasure of memory with participation of nitroxide is experimentally and theoretically based.     

Selection for associative learning of color stimuli reveals correlated evolution of this learning ability across multiple stimuli and rewards

We are only starting to understand how variation in cognitive ability can result from local adaptations to environmental conditions. A major question in this regard is to what extent selection on cognitive ability in a specific context affects that ability in general through correlated evolution. To address this question, we performed artificial selection on visual associative learning in female Nasonia vitripennis wasps. Using appetitive conditioning in which a visual stimulus was offered in association with a host reward, the ability to learn visual associations was enhanced within 10 generations of selection. To test for correlated evolution affecting this form of learning, the ability to readily form learned associations in females was also tested using an olfactory instead of a visual stimulus in the appetitive conditioning. Additionally, we assessed whether the improved associative learning ability was expressed across sexes by color‐conditioning males with a mating reward. Both females and males from the selected lines consistently demonstrated an increased associative learning ability compared to the control lines, independent of learning context or conditioned stimulus. No difference in relative volume of brain neuropils was detected between the selected and control lines.     

Dynamic Spatial Organization of Receptive Fields of Neurons in the 21a Cortical Area

We studied changes in the spatial parameters of receptive fields (RFs) of visually sensitive neurons in the associative area 21a of the cat cortex under conditions of presentation of moving visual stimuli. The results of experiments demonstrated that these parameters are dynamic and depend, from many aspects, on the pattern of the stimulus used for their estimation. Angular lengths of the horizontal and vertical axes of the RFs measured in the case of movement of the visual stimuli exceeded many times those determined by presentation of stationary blinking stimuli. As is supposed, a visual stimulus, when moving along the field of vision, activates a certain number of the neurons synaptically connected with the examined cell and possessing RFs localized along the movement trajectory. As a result, such integrated activity of the neuronal group can change the excitation threshold and discharge frequency of the studied neuron. It seems probable that correlated directed activation of the neuronal groups represents a significant neurophysiological mechanism providing dynamic modifications of the RF parameters of visually sensitive neurons in the course of processes of visual perception and identification of moving objects within the field of vision.     

Flavor Preference Learning Increases Olfactory and Gustatory Convergence onto Single Neurons in the Basolateral Amygdala but Not in the Insular Cortex in Rats

The basolateral amygdala (BLA) and the insular cortex (IC) represent two major areas for odor-taste associations, i.e. flavor integration. This learning may require the development of convergent odor and taste neuronal activation allowing the memory representation of such association. Yet identification of neurons that respond to such coincident input and the effect of flavor experience on odor-taste convergence remain unclear. In the present study we used the compartmental analysis of temporal activity using fluorescence in situ hybridization for Arc (catFISH) to visualize odor-taste convergence onto single neurons in the BLA and in the IC to assess the number of cells that were co-activated by both stimuli after odor-taste association. We used a sucrose conditioned odor preference as a flavor experience in rats, in which 9 odor-sucrose pairings induce a reliable odor-taste association. The results show that flavor experience induced a four-fold increase in the percentage of cells activated by both taste and odor stimulations in the BLA, but not in the IC. Because conditioned odor preference did not modify the number of cells responding selectively to one stimulus, this greater odor-taste convergence into individual BLA neurons suggests the recruitment of a neuronal population that can be activated by both odor and taste only after the association. We conclude that the development of convergent activation in amygdala neurons after odor-taste associative learning may provide a cellular basis of flavor memory.