A Model of Self-Organizing Head-Centered Visual Responses in Primate Parietal Areas

We present a hypothesis for how head-centered visual representations in primate parietal areas could self-organize through visually-guided learning, and test this hypothesis using a neural network model. The model consists of a competitive output layer of neurons that receives afferent synaptic connections from a population of input neurons with eye position gain modulated retinal receptive fields. The synaptic connections in the model are trained with an associative trace learning rule which has the effect of encouraging output neurons to learn to respond to subsets of input patterns that tend to occur close together in time. This network architecture and synaptic learning rule is hypothesized to promote the development of head-centered output neurons during periods of time when the head remains fixed while the eyes move. This hypothesis is demonstrated to be feasible, and each of the core model components described is tested and found to be individually necessary for successful self-organization.     

Attentional diversion during adaptation affects the velocity as well as the duration of motion after-effects

The effects of diverting attention on early motion processing in human vision were studied with a selective adaptation technique. The velocity of motion after-effects (MAEs) produced on a stationary test grating after prolonged exposure to drifting luminance-modulated gratings was measured by matching MAE velocity with that of another physically moving grating. Initial MAE velocities decreased and their rate of decay increased with the distance of the adapting and test gratings from the fixation point. When attention was diverted from the adapting grating, by having subjects process the intermittently changing digit which formed the fixation point, initial MAE velocities were reduced and rate of decay increased, with the largest effect of diversion being found for gratings near the fixation point. The effects of varying attention mimic those of varying adapting duration, rather than adapting contrast or velocity, and appear to reflect a genuine change in motion-processing mechanisms.     

A neural network model of the McCollough effect

A self-organizing, feature-extracting network (von der Malsburg, 1973) is extended to two feature dimensions to encompass line orientation and color. It is applied to McCollough effects, particularly longlasting, contingent-aftereffects. McCollough effects are thought to involve low-level associative memory in the form of synaptic modification. The McCollough-Malsburg Model (MMM) embodies positive synaptic modification with correlated firing of units in an input layer and an excitatory cortical layer. Computer simulation of MMM reproduces orientation-contingent color aftereffects. The model embodies many of the mechanisms thought to be operating in developmental plasticity, suggesting that equivalent mechanisms may be involved in adult long-term adaptation as well.This work was supported in part by NIH Grant No. 5 R01 NS09755-4 COM of the National Institute of Neurological Diseases and Stroke (M.A. Arbib, Principal Investigator)     

Long-term modifications in the strength of excitatory associative inputs in the piriform cortex

Afferent olfactory information, in vivo and in vitro, can be rapidly adapted to through a metabotropic glutamate receptor (mGluR)-mediated attenuation of synaptic strength. Specific cellular and synaptic mechanisms underlying olfactory learning and habituation at the cortical level remain unclear. Through whole-cell recording, excitatory postsynaptic currents (EPSCs) were obtained from piriform cortex (PC) principal cells. Using a coincidental, pre- and postsynaptic stimulation protocol, long-term depression (LTD) in synaptic strength was induced at associative, excitatory synapses onto layer II pyramidal neurons of the mouse (P15-27) PC. LTD was mimicked and occluded by mGluR agonists and blocked by nonselective mGluR antagonist (RS)-alpha-methyl-4-sulfonophenylglycine (MSPG) but not by N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Analysis of the paired-pulse ratio, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA current ratio, and spontaneous EPSCs indicate that electrically induced LTD was mediated predominantly by postsynaptic mechanisms. Additionally, presynaptic mGluRs were involved in agonist-mediated synaptic depression. Immunohistochemical analysis supports the presence of multiple subclasses of mGluRs throughout the PC, with large concentrations of several receptors present in layer II. These observations provide further evidence of activity-dependent, long-term modification of associative inputs and its underlying mechanisms. Cortical adaptation at associative synapses provides an additional link between cortical olfactory processing and subcortical centers that influence behavior.     

RNA conformation in rod-shaped viruses: a possible molecular model for RNA in narcissus mosaic virus.

A model for visual adaptation to spatial grating is developed based on the assumption that inhibitory synapses within the visual system may be temporarily modified as a function of recent usage. Specifically, it is hypothesized that inhibitory synaptic weights are altered as a function of the correlation between recent presynaptic and postsynaptic activity. When such modifiable synapses are incorporated into a simple neural network model having the spatial filtering properties of the human visual system, two coupled equations are obtained which may be solved analytically. The model accounts for experimental data on adaptation to sinusoidal gratings, square wave gratings, single bars, and tilted gratings. The relationship of the model to single and multiple channel models of the human visual system is discussed.     

A synaptic model for spatial frequency adaptation

A model for visual adaptation to spatial grating is developed based on the assumption that inhibitory synapses within the visual system may be temporarily modified as a function of recent usage. Specifically, it is hypothesized that inhibitory synaptic weights are altered as a function of the correlation between recent presynaptic and postsynaptic activity. When such modifiable synapses are incorporated into a simple neural network model having the spatial filtering properties of the human visual system, two coupled equations are obtained which may be solved analytically. The model accounts for experimental data on adaptation to sinusoidal gratings, square wave gratings, single bars, and tilted gratings. The relationship of the model to single and multiple channel models of the human visual system is discussed.     

A neurocomputational model of stimulus-specific adaptation to oddball and Markov sequences

Stimulus-specific adaptation (SSA) occurs when the spike rate of a neuron decreases with repetitions of the same stimulus, but recovers when a different stimulus is presented. It has been suggested that SSA in single auditory neurons may provide information to change detection mechanisms evident at other scales (e.g., mismatch negativity in the event related potential), and participate in the control of attention and the formation of auditory streams. This article presents a spiking-neuron model that accounts for SSA in terms of the convergence of depressing synapses that convey feature-specific inputs. The model is anatomically plausible, comprising just a few homogeneously connected populations, and does not require organised feature maps. The model is calibrated to match the SSA measured in the cortex of the awake rat, as reported in one study. The effect of frequency separation, deviant probability, repetition rate and duration upon SSA are investigated. With the same parameter set, the model generates responses consistent with a wide range of published data obtained in other auditory regions using other stimulus configurations, such as block, sequential and random stimuli. A new stimulus paradigm is introduced, which generalises the oddball concept to Markov chains, allowing the experimenter to vary the tone probabilities and the rate of switching independently. The model predicts greater SSA for higher rates of switching. Finally, the issue of whether rarity or novelty elicits SSA is addressed by comparing the responses of the model to deviants in the context of a sequence of a single standard or many standards. The results support the view that synaptic adaptation alone can explain almost all aspects of SSA reported to date, including its purported novelty component, and that non-trivial networks of depressing synapses can intensify this novelty response.     

Priming of associative long-term depression in the dentate gyrus by theta frequency synaptic activity.

Associative long-term synaptic depression (LTD) was investigated utilizing negatively correlated activity patterns in the medial and lateral perforant path inputs to the dentate gyrus in anesthetized rats. Normally only nonassociative, or heterosynaptic, LTD is elicited in naive pathways. We report here, however, that associative LTD in the lateral path is readily induced after being "primed" by a brief period of lateral path synaptic activity at a theta rhythm frequency (5 Hz). Priming of associative LTD lasts at least 2 hr and is not seen following priming activity at non-theta frequencies (1 and 15 Hz). N-methyl-D-aspartate receptor activation is critical for establishing the priming effect, but not for the subsequent induction of the associative LTD. These data suggest that theta rhythm activity in the dentate gyrus may predispose the system to a specific form of synaptic plasticity, associative LTD.     

After-effects and the integration of patterns of neural activity within a channel

Prolonged inspection of an adapting simulus changes the appearance of a subsequent test stimulus. There are five distinct viewing conditions under which such 'after-effects' may be generated. There are MON-MON (inspect with one eye, same eye), BIN-BIN (inspect with both eyes, test both eyes), BIN-MON (inspect with both eyes, test only one eye), MON-BIN (inspect with one eye, test with both) and TRANSFER (inpect with one eye, test with the other eye). A model based upon the assumption of the linearly additive effects of adaptation generated in 'dominance classes' or cortical units that are driven either by one eye, or the other eye, or by either or both eyes together, is described. This model generates predictions concerning the expected ralative magnitudes of after-effects generated under the five viewing modes described above, and experiments are described that confirm these predictions. The model can be extended to gaenerate predictions about other experimental conditions. A more complex version of the model is consistent with electrophysiologically derived estimates of the proportion of cortical units in each dominance class.     

Acetylcholine and associative memory in the piriform cortex

The significance of cholinergic modulation for associative memory performance in the piriform cortex was examined in a study combining cellular neurophysiology in brain slices with realistic biophysical network simulations. Three different physiological effects of acetylcholine were identified at the single-cell level: suppression of neuronal adaptation, suppression of synaptic transmission in the intrinsic fibers layer, and activity-dependent increase in synaptic strength. Biophysical simulations show how these three effects are joined together to enhance learning and recall performance of the cortical network. Furthermore, our data suggest that activity-dependent synaptic decay during learning is a crucial factor in determining learning capability of the cortical network. Accordingly, it is predicted that acetylcholine should also enhance long-term depression in the piriform cortex.     

Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits.

Febrile (fever-induced) seizures affect 3-5% of infants and young children. Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial. Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood. The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions.     

Late EEG after-effects in humans following hyperventilation. II. A comparison between subjects with different level of adaptation to hypoxia

The late EEG after-effects following application of a short-lasting ventilatory interoceptive influence (3 min hyperventilation-HV) were studied in humans with three degrees of adaptation: students (ST) with a lower degree of training, professional alpine climbers with a high level of training (AL1) and the same subjects (AL2) in a middle position of adaptation i.e. 6 months after an expedition. ST developed late EEG after-effects, consisting mainly in an increase of the beta-2 EEG activity; AL1 showed very slight changes, while in AL2 the EEG after-effects were intermediate. It is suggested, that a lower level of adaptation facilitates the triggering through HV of processes in the cortical EEG which accompany an improvement of the brain tone.     

Adaptation to contingencies in macaque primary visual cortex.

We tested the hypothesis that neurons in the primary visual cortex (V1) adapt selectively to contingencies in the attributes of visual stimuli. We recorded from single neurons in macaque V1 and measured the effects of adaptation either to the sum of two gratings (compound stimulus) or to the individual gratings. According to our hypothesis, there would be a component of adaptation that is specific to the compound stimulus. In a first series of experiments, the two gratings differed in orientation. One grating had optimal orientation and the other was orthogonal to it, and therefore did not activate the neuron under study. These experiments provided evidence in favour of our hypothesis. In most cells adaptation to the compound stimulus reduced responses to the compound stimulus more than it reduced responses to the optimal grating, and the responses to the compound stimulus were reduced more by adaptation to the compound stimulus than by adaptation to the individual gratings. This suggests that a component of adaptation was specific to (and caused by) the simultaneous presence of the two orientations in the compound stimulus. To test whether V1 neurons could adapt to other contingencies in the stimulus attributes, we performed a second series of experiments, in which the component gratings were parallel but differed in spatial frequency, and were both effective in activating the neuron under study. These experiments failed to reveal convincing contingent effects of adaptation, suggesting that neurons cannot adapt equally well to all types of contingency.     

Vector representation of associative learning

I. P. Pavlov [12] has shown that conditioned reflexes are selective both with respect to conditioned stimuli and to conditioned reflexes elicited by those conditioned stimuli. At the neuronal level selective aspects of conditioned stimuli are based on detectors selectively tuned to respective stimuli. The selective aspects of conditioned reflexes are due to command neurons representing specific unconditioned reflexes. It can be assumed that conditioned reflexes result from association between selective detectors and specific command neurons. The detectors activated by a conditioned stimulus constitute a combination of excitations--a detector excitation vector. The detector excitation vector acts on a command neuron via a set of plastic synapses--a synaptic weight vector. Plastic synapses are modified in the process of learning making command neuron selectively tuned to a specific conditioned stimulus. The selective tuning of a particular command neuron to a specific excitation vector referred to a conditioned stimulus is a basis of associative learning. The probabilities of conditioned reflexes elicited by conditioned and differential stimuli implicitly contain information concerning excitation vectors that encode respective stimuli. Contribution of the vector code to associative learning was explored combining differential color conditioning with intracellular recording from color-coding neurons. It was shown that colors in carps and monkeys are represented on a hypersphere in the four-dimensional space similar to human color space. The basis of the color space is constituted by red-green, blue-yellow, brightness and darkness neurons.     

Reinforcement pre-exposure enhances spatial memory formation in <Emphasis Type="Italic">Drosophila</Emphasis>

Apparently unpaired exposure to appetitive or aversive stimuli can suppress or enhance later associative learning. While the suppressive effect has been found in both vertebrate and invertebrate animals, it is not clear if the enhancing effect is restricted to the vertebrates. Additionally, whether Drosophila associative learning can be influenced in either direction is open. To address these questions, we examined the effects of pre-exposing flies to a high temperature negative reinforcer in the heat-box place-learning paradigm. We found that pre-exposing flies to an unavoidable high temperature enhanced later associative conditioning that uses mild increases in temperature. This enhancement lasts at least 20 min, does not depend on changes in the straightforward avoidance behavior of a high temperature source, and is independent of the antennal thermosensor. We thus provide an example of enhanced associative learning after unpaired exposure to a typical reinforcer in an invertebrate animal, suggesting the conservation of this component of learning.     

The effect of temperature acclimation on NADP-dependent dehydrogenase activity in the carp liver and various mechanisms of its regulation

Acclimation of carp both to the temperature fall (from 20 to 5 degrees C) and rise (from 20 to 30 degrees C) induces an increase in activity of cytoplasmic liver NADPH-generating enzymes--glucose-6-phosphate dehydrogenase (G6PDG) and malic-enzyme (ME) 6-phosphogluconate dehydrogenase (6PGDG) and NADP-isocitrate dehydrogenase (NADP-IDG) activities are unchanged. Actinomycin D does not prevent cold activation of G6PDG but blocks activation of ME. "Warm" G6PDG has minimal Km value for glucose-6-phosphate and "warm" ME has minimal Km value for glucose-6-phosphate and "warm" ME has minimal Km value for malate at 25 degrees C "Cold" G6PDG and ME have the warmest Km values at 5 degrees C. Isozyme composition of cytoplasmic G6PDG (2 bands with Rf 0.16 and 0.20) does not change within the limits of 5-30 degrees C. The prolactin action on G6PDG and ME is similar to the effect of cold acclimation (activity increases Km value decreases, isozyme pattern (for G6PDG) remains unchanged). It is supposed that activation of G6PDG and ME during cold adaptation may be a result of the prolactin action on substrate-binding ability without changes in the enzyme biosynthesis and isozyme pattern.     

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.