Mechanisms Of Habituation Research Articles

Modeling the dishabituation hierarchy: the role of the primordial hippocampus.

We present a neural model for the organization and neural dynamics of the medial pallium, the toad's homolog of mammalian hippocampus. A neural mechanism, called cumulative shrinking, is proposed for mapping temporal responses from the anterior thalamus into a form of population coding referenced by spatial positions. Synaptic plasticity is modeled as an interaction of two dynamic processes which simulates acquisition and both short-term and long-term forgetting. The structure of the medial pallium model plus the plasticity model allows us to provide an account of the neural mechanisms of habituation and dishabituation. Computer simulations demonstrate a remarkable match between the model performance and the original experimental data on which the dishabituation hierarchy was based. A set of model predictions is presented, concerning mechanisms of habituation and cellular organization of the medial pallium.

Correlates of Habituation of a Polysynaptic Reflex in Crayfish In Vivo and In Vitro.

Reflex leg levation habituates during repeated electrical stimulation of mechanosensory afferents in the dactyl of the fifth walking leg of the crayfish, Procambarus clarkii. This was investigated in decerebrate crayfish, and reproduced in an isolated thoracic ganglion preparation. In vivo, trains of stimuli delivered every 2.5 s produced a gradual decrease in the amplitude of the mechanical response, and a concomitant decrease in the number of impulses per burst in the levator muscle myogram. Near complete recovery occurred after 10 min rest, and transient dishabituation was observed after electrical stimulation of the telson. Less frequent or stronger stimuli led to less rapid habituation. In vitro, the same parametric characteristics of habituation were observed in the levator nerve responses, while the intrinsic variability of the reflex was reduced. The response decrement was shown to be unrelated to changes in the afferent excitation. Evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in levator motorneurons decreased in parallel with the levator neurogram. This decrease was unrelated to any change in the resting membrane potential of the levator motorneurons. Interneurons with habituating EPSPs, antagonistic depressor motorneurons with habituating inhibitory postsynaptic potentials and non-habituating responses in other motorneuronal groups were also found. These findings point to a central locus of habituation upstream from the motorneurons, and offer prospects for a detailed investigation of the mechanisms of habituation in a polysynaptic system.

Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender, instruction, personality and placebo

Two experiments are described which evaluate the role of associative mechanisms and placebo effects on aversively conditioned skin conductance responses in groups of healthy volunteers. In both experiments, skin conductance level (SCL), variability (spontaneous fluctuations, SF) and amplitude (SCR) were recorded during a sequence of tone stimuli (80 dB, 1 s, 360 Hz). All the variables habituated during the first ten presentations of the tones. Tone 11 was immediately followed by a loud (100 dB) aversive brief (1 s) white noise UCS. The conditioning trial significantly enhanced SCRs to a further ten presentations of the tones and increased SCL and variability (SF). No enhancement of SCRs occurred when tone 11 was omitted and the UCS occurred in temporal isolation (experiment 1). Thus enhanced SCRs to tones following paired tone-noise presentation involves an associative mechanism. Increased "spontaneous" variability was shown to involve both conditioning and sensitization following the UCS. In both experiments females showed greater conditioned SCRs than males. In experiment 2 no effect of "anxiolytic" placebo could be discerned and there were no general relationships between questionnaires scores of extraversion or neuroticism with skin conductance measures in a group of 40 volunteers. The results question the role of conditionability and autonomic lability as major determinants of extraversion and neuroticism. These studies validate the use of the psychophysiological model of aversive conditioning in pharmacological studies of the mechanisms of habituation, conditioning and sensitization.

Evaluation of a psychophysiological model of classical fear conditioning in anxious patients

Skin conductance variables have been compared in 30 anxious patients and 30 controls to investigate the extent to which anxiety is associated with increased autonomic arousal, reduced habituation or enhanced aversive conditioning. Skin conductance level, variability (spontaneous fluctuations) and response amplitudes to tones were significantly greater in patients than controls. Habituation of skin conductance responses to a series of ten innocuous tones (80 dB, 1 s) did not differ between the groups. Aversively conditioned skin conductance responses were measured to a further series of ten tones after a conditioning trial in which a loud white noise (100 dB) followed tone 11. All subjects showed enhanced (conditioned) responses to the tones after the conditioning trial, but patients did not show greater conditioning than controls. The results indicate that anxious neurotic out-patients have greater sweat gland activity and reactivity than controls but fail to demonstrate differences in central mechanisms of habituation or conditioning.

Silicon models of associative learning in Aplysia

Relatively simple invertebrate animals exhibit an impressive variety of learning and memory behaviour including such associative learning tasks as classical or Pavlovian conditioning. The cellular machinery responsible for this behaviour is beginning to be understood by neurophysiologists in certain well-studied species such as the marine mollusc Aplysia. We describe analog CMOS circuits which can be used to qualitatively mimic the mechanisms of associative learning in this creature. In particular we model the synaptic plasticity and activity-dependent facilitation in sensorimotor synapses responsible for classical conditioning of the gill withdrawal reflex. The same circuits implement the nonassociative learning mechanisms of habituation and sensitization. We also discuss considerations in abstracting from the biological mechanisms when developing artificial neural systems. The specific circuits for Aplysia described in this paper are suggestive of ways to implement VLSI area-efficient associative learning circuits in general, especially those which perform in situ temporal associations on multiple synaptic inputs.

Effects of Anti-cholinergic and Cholinergic Drugs on Habituation to Motion in Rats

The effects of the anti-cholinergic drug scopolamine, an anti-motion sickness drug, and of the cholinergics physostigmine and neostigmine on habituation to motion sickness in rats were examined using pica, measured as eating of kaolin, as a behavioural index of motion sickness in rats. Rats were rotated around two axes for 1 h once a day for 10 or 11 days. Rotation-induced kaolin intake of control rats gradually decreased from day 9 of daily rotation. Test rats were not treated for the first 3 days, given drugs on days 4-7 of rotation and then again given no drugs for the next 3 or 4 days. Rotation-induced kaolin intake of test rats was compared to that of controls. Results showed that TTS (Transdermal Therapeutic System)-scopolamine administration facilitated habituation to rotation, whereas physostigmine, a centrally acting cholinesterase inhibitor, suppressed it, and neostigmine, a peripherally active cholinesterase inhibitor, had no effect on habituation at all. These findings suggest that the central cholinergic neuron system plays an important role in the neural mechanism of habituation to motion in rats.

Mechanisms of attention: A developmental study

A model of selective attention is proposed which contains a number of properties. First, stimuli which are irrelevant to the subjects' task can be analyzed to semantic levels automatically, and such stimuli can produce intrusion/interference effects. Second, two mechanisms by which selection is achieved are habituation to, and inhibition of, these irrelevant stimuli. A series of studies demonstrates that both the ability to process automatically irrelevant stimuli and the habituation mechanisms of attention are observable by Grade 2, whereas the inhibitory mechanism is not always evident at this stage. It is suggested that the greater distractability of children in certain situations may be due in part to the underutilization of this inhibitory mechanism. We further propose that children may be able to employ inhibitory mechanisms in more familiar perceptual-motor tasks.

Involvement of group S-100 brain specific proteins in the neurophysiological mechanisms of habituation

The possible role of S-100 brain specific proteins and their involvement in the neuronal mechanisms of habituation were investigated in identified neurons of the snail (Helix pomatia). Extracellular application and intracellular injection of antibodies into S-100 proteins caused a rapid and significant reduction of neuronal response to repeated stimulation compared with the control. A considerable reduction in the amplitude of evoked EPSP and an increase in the duration of latency of potentials was produced by the antibodies and numbers of action potentials declined. Meanwhile, membrane potential, membrane input impedance, and neuronal pacemaker potentials remained virtually unchanged. This effect is presumed to occur due to breakdown of synaptic transmission processes. The subject of possible involvement of S-100 proteins in the operation of synaptic structures as a primary apparatus for integrating neuronal activity is considered.

Associative and non-associative tolerance to morphine: Support for a dual-process habituation model

Some unique predictions of a dual-process habituation model of morphine analgesic tolerance were examined concerning the interactions of drug-signal conditions and dose/frequency parameters. The model assumes that tolerance is the result of a combination of associative and non-associative habituation mechanisms which are differentially affected by dose and drug-signal conditions. In accordance with predictions of the model, low doses and long interdrug intervals (IDI's) resulted in faster tolerance acquisition, greater tolerance retention, and higher levels of associative tolerance, than high doses and short IDI's. Alternative accounts of tolerance based on Pavlovian conditioning mechanisms cannot explain this pattern of results. The question of generality of these findings to other drugs and other response measures is discussed.

Human cerebral potentials evoked by CO2 laser stimuli causing pain.

Brief radiant heat pulses, generated by a CO2 laser, were used to activate slowly conducting afferents in the hairy skin in man. In order to isolate C-fibre responses a preferential A-fibre block was applied by pressure to the radial nerve at the wrist. Stimulus estimation and evoked cerebral potentials (EP), as well as reaction times, motor and sudomotor activity were recorded in response to each stimulus. With intact nerve, the single supra-threshold stimulus induced a double pain sensation: A first sharp and stinging component (mean reaction time 480 ms) was followed by a second burning component lasting for seconds (mean reaction time 1350 ms). Under A-fibre block only one sensation remained with characteristics and latencies of second pain. The heat pulse evoked potential consisted of a late vertex negativity at 240 ms (N240) followed by a prominent late positive peak at 370 ms (P370). Later activity was not reliably present. Under A-fibre block this late EP was replaced by an ultralate EP beyond 1000 ms, which in the conventional average looked like a slow halfwave of 800 ms duration. This potential was distinct from eye movements, skin potentials or muscle artefacts. With cross-correlation methods waveforms similar to the N240/P370 were detected in the latency range from 900 to 1500 ms during A-fibre block, indicating a much greater latency jitter of the ultralate EP. Latency corrected averaging with a modified Woody filter yielded a grand mean ultralate EP (N1050/P1250), the shape of which was surprisingly similar to the late EP (N240/P370). The similarity of these components indicates that both EPs may be secondary responses to afferent input into neural centers, onto which myelinated and unmyelinated fibres converge. Such convergence may also explain through the known mechanisms of short term habituation and selective attention, why ultralate EPs are not reliably present without peripheral nerve block.

Synaptic plasticity in vitro: cell culture of identified Aplysia neurons mediating short-term habituation and sensitization

The gill withdrawal reflex of the marine mollusk, Aplysia californica, shows habituation and sensitization, two simple forms of learning. In order to extend the cellular studies on synaptic plasticity underlying the changes in the reflex behavior, and to explore further the development of synaptic plasticity during synapse formation, we have sought to establish the neural circuit of the gill withdrawal reflex in vitro. We report here the reconstruction of the elementary gill withdrawal circuit in cell culture and find that the cells show short-term homosynaptic depression and heterosynaptic facilitation, the cellular mechanisms of habituation and sensitization, respectively.

Development of plastic mechanisms related to learning at identified chemical synaptic connections in Aplysia

In the marine snail Aplysia californica learned changes in behavior have been traced to alterations in synaptic efficacy. With the ability to raise the animals in the laboratory, we have explored the development of four types of plastic mechanisms at identified synapses: post-tetanic potentiation and pre-synaptic inhibition, which do not as yet have known behavioral functions, and homosynaptic depression, the cellular mechanism of short-term habituation, and heterosynaptic facilitation, the basis of short-term sensitization. Homosynaptic depression and pre-synaptic inhibition are present early in juvenile life. In contrast, post-tetanic potentiation and heterosynaptic facilitation appear only later, after a discrete interval. The step-wise ontogeny of synaptic plastic mechanisms in Aplysia parallels the gradual emergence of behavior in successive developmental stages. Interestingly, sensescence reverses the developmental sequence for habituation and sensitization mechanisms. To pursue further an understanding of the relationship between synapse formation and plasticity underlying learning it will be necessary to extend these studies to dissociated cell culture where mechanisms can be explored on the molecular level. Cell culture may also permit examination of the development of cellular mechanisms underlying classical and operant conditioning which may clarify differences between associative and non-associative mechanisms.

A neural theory of circadian rhythms: Split rhythms, after-effects and motivational interactions

A neural theory of the circadian pacemaker within the hypothalamic suprachiasmatic nuclei (SCN) is used to explain parametric data about mammalian operant behavior. The intensity, duration, and patterning of ultradian activity-rest cycles and the duration of circadian periods due to parametric (LL) and nonparametric (LD) lighting regimes are simulated. Paradoxical data about split rhythms and after-effects are explained using homeostatic and nonhomeostatic neural mechanisms that modulate pacemaker activity. These modulatory mechanisms enable the pacemaker to adjust to pervasive changes in its lighting regime, as during the passage of seasons, and to ultradian changes in internal metabolic conditions. The model circadian mechanisms are homologous to mechanisms that model hypothalamically mediated appetitive behaviors, such as eating. The theory thus suggests that both circadian and appetitive hypothalamic circuits are constructed from similar neural components. Mechanisms of transmitter habituation, opponent feedback interactions between on-cells and off-cells, homeostatic negative feedback, and conditioning are used in both the circadian and the appetitive circuits. Output from the SCN circadian pacemaker is assumed to modulate the sensitivity of the appetitive circuits to external and internal signals by controlling their level of arousal. Both underarousal and overarousal can cause abnormal behavioral syndromes whose properties have been found in clinical data. A model pacemaker can also be realized as an intracellular system.

Possible mechanisms of dendritic potential habituation in the cat association cortex

The effect of application of strychnine and calcium and of post-tetanic potentiation on the dynamics of gradual decay of dendritic potentials in the association cortex, which is regarded as monosynaptic habituation, was studied in acute experiments on cats anesthetized with pentobarbital. Despire a significant increase in amplitude of dendritic potentials after strychnine application or calcium enrichment of the physiological saline, the time course of habituation was unchanged. The course of habituation also remained unchanged during post-tetanic potentiation. It is concluded that habituation of dendritic potentials is due to processes taking place in the postsynaptic dendrite membrane itself and is independent of postsynaptic inhibition or transmitter exhaustion in presynaptic endings.

Habituation of the acoustic startle response in rats after lesions in the mesencephalic reticular formation or in the inferior colliculus.

Extensive damage to the mesencephalic reticular formation (MRF) in rats altered long-term habituation of the acoustic startle response without disrupting short-term habituation. The MRF lesions did not alter initial startle amplitudes, but the animals with lesions were unable to attain as low a long-term asymptote of habituation as could control animals. Subsequent manipulation of stimulus intensity and interstimulus interval revealed no differences in short-term habituation between the two groups. Large lesions to the inferior colliculus (IC) did not disrupt long-term habituation of the acoustic startle response, but these animals were unable to suppress responding as much as controls to intense stimuli presented rapidly. The deficits in long-term habituation following MRF lesions suggested a disruption of an extrinsic, inhibitory mechanism of habituation. The deficits following IC lesions could be due either to a disruption of a short-term habituation mechanism or to an increase in response sensitization produced by the lesions.

Species-typical IRMs in CA1-3 hippocampi and habituation memory in area dentata

Sector CA3c hippocampi contains the genetically preprogrammed innate releaser mechanisms (IRMs) for species-typical threats; CA3b a the genetically preprogrammed innate releaser mechanisms for species-typical nutrients, playmates and surroundings. Activation of these mechanisms, whilst triggering species-appropriate motor responses via the fornix and the mammillo-tegmental tract, teaches the meaningfulness of the recognized patterns, via the mammillo-thalamic tract, into the neocortex which is unprogrammed genetically but passively files all percepts transmitted via the thalamic sensory relay nuclei. Sector CA1 contains the genetically preprogrammed innate releaser mechanisms for mating and parenting, but becomes available only after hormonal activation of its circuitry at puberty. Area dentata, with boosting from the medial septal theta system, automatically filters-out from transmission into CA most once-attended patterns which CA3 has not recognized. The filtered patterns are filed within area dentata, ie. area dentata automatically builds a memory bank of percepts not requiring motor reaction, including a conceptual map of the habitat. Desynchronization of the theta system by reward or punishment signals from the brainstem, in response to some once-attended novel patterns, halts the filter-file habituation mechanism, permitting some early-life learning of non-innate releaser patterns to be added to CA3c and CA3b a . In adulthood the relatively redundant ammonshorn may continue to be activated in parallel with the immensely more versatile neocortex, and the fornices may be bilaterally transected with relative impunity.

Disruption of vertebrate monosynaptic habituation by ethyl alcohol

The effects of ethyl alcohol on neuronal plasticity were examined using a model systems preparation of monosynaptic habituation: the lateral column to motoneuron pathway of the isolated frog spinal cord. Two fundamental effects of alcohol on this system were demonstrated. First, alcohol always depressed the ventral root responses to lateral column stimulation when stimulus intensity was held constant across conditions. This was accompanied by an increase in the amount of habituation produced as training progressed. Second, when stimulus intensity was increased in the alcohol condition so that responses were equated with pre-alcohol response amplitudes, the amount of habituation was markedly decreased. Results are discussed both in terms of proposed mechanisms of habituation and of possible pharmacological interactions with this simple example of response plasticity.

Changes in input resistance of a cortical neuron and in threshold of stimulation of its electrically excitable membrane by a depolarizing current during habituation.

1. Habituation of visual cortical neurons in the turtle forebrain is accompanied by a change in their input resistance. The input resistance of the neuron during the action of a monotonous stimulus falls in the course of habituation, but at the time of action of an extrastimulus it rises. At the time of action of a monotonous stimulus it is restored after an extrastimulus and also spontaneously after an interruption. 2. Habituation of visual cortical neurons in the turtle forebrain is accompanied by a change in thresholds of stimulation of the electrically excitable membrane by a depolarizing current. During the development of habituation the threshold of stimulation rises if the depolarizing current is a monotonous stimulus, and it falls if the depolarizing current is an extrastimulus. The threshold to a monotonous stimulus is restored after an extrastimulus and spontaneously after an interruption. 3. Changes in the input resistance of a cortical neuron and in the threshold of stimulation of its electrically excitable membrane by a depolarizing current are specific relative to the stimulus, they take place during its action, and they are reversible. These are postsynaptic mechanisms of habituation.

Etude quantitative de la rétention de l'habituation de la réponse optocardiaque chez Calliphora vomitoria (Dipt. Calliphoridae)

Retention of habituation has been studied in blowflies which had received different numbers of visual stimulations during acquisition, and tested after various rest intervals by a second series of trials. The results showed that it was necessary to quantify retention by means of two parameters, one measuring spontaneous recovery of the response, the other valuating the rate of subsequent rehabituation. They did not show the same temporal dynamic and they are not influenced in the same way by the amount of previous stimulations. The analysis of correlations between acquisition and retention parameters confirmed their relative independancy. According to these results and to current knowledge of habituation mechanisms, a model is proposed assuming that short-term retention of habituation proceeds from a transient functional alteration of the state of the response system, lowering its responsiveness. Long-term retention, only shown by a faster rate of rehabituation would result from a more persistent impairment of the mechanisms involved in the restoration over time of the reactivity state of the response system.

Mechanisms of habituation of the electrically excitable membrane of the cortical neuron.

1. Excitability of the electrically excitable membrane of the cortical neuron changes regularly in the course of habituation to a repetitive stimulus. 2. Excitability of the trigger zones of the spontaneous AP increases nonspecifically, due to nonspecific depolarization of the membrane. 3. Excitability of the trigger zones of AP evoked by a monotonic stimulus and an extrastimulus changes in opposite directions. The critical level of depolarization of AP in response to a monotonic stimulus shifts in the positive direction, and its threshold potential rises. The critical level of depolarization of AP in response to an extrastimulus shifts in the negative direction and its threshold potential falls. 4. Lowering of the excitability of the trigger zones generating AP in response to a monotonic stimulus and the increase in excitability of zones participating in AP generation in response to an extrastimulus are the postsynaptic mechanism of habituation of the electrically excitable membrane of the cortical neuron. 5. Changes in the electrogenic properties of the trigger zones of evoked AP are the probable cause of functional lability of the excitability of these zones during habituation.