Tactile Conditioned Stimulus Research Articles

Behavioral verification of associative learning in whiskers-related fear conditioning in mice.

Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most of the Pavlovian conditioning paradigms auditory stimulus is used as a conditioned stimulus (CS), but conditioning can be accomplished also to tactile CS. The whisker-to-barrel tactile system in mice offers convenient way to investigate the brain pathways and mechanisms of learning, and plasticity of the brain cortex. To support a claim that an animal learns during conditioning session and that the plastic changes are associative in nature, objective measures of behavior are necessary. Multiple types of conditioned responses can develop, depending on the training situation, CS and unconditioned stimulus (UCS) characteristics. These include physiological responses, such as salivation, heart rate, galvanic skin reaction, and also behavioral responses, such as startle reflex potentiation or suppression of the ongoing behavior. When studying learning with the whisker system in behaving mice, stimulation of individual whiskers in a well-controlled manner may require animal restrain with a disadvantage of only limited behavioral responses observed. Stimulation of whiskers in the neck-restraining apparatus evokes head movements. When whiskers stimulation (CS) is paired with an aversive UCS during conditioning, the head movements decrease in the course of the training. This reaction, called minifreezing, resembles freezing response, frequently used behavioral measure, however applicable only in freely moving animals. This article will review experimental evidences confirming that minifreezing is a relevant index of association formation between the neutral CS and the and the aversive UCS.

Conditioned preferences and aversions in infant rats mediated through ethanol inhalation

Little is known about the acute motivational effects of inhaled ethanol during early postnatal development. We analyzed the motivational properties of ethanol inhalation in infant rats by using two distinct schedules of ethanol vapor delivery. Ethanol was presented in a continuous conditioning trial or in separate, distributed trials. Maximum blood ethanol concentrations (BECs) induced by these schedules were 55 and 15 mg%, respectively (Experiment 1). In Experiment 2, subjects were given daily pairings (postnatal days [PD] 14 and 15) between a tactile conditioned stimulus (CS, sandpaper) and the postabsorptive effects of ethanol inhalation. A tactile preference test (PD16) revealed a significant aversion for the CS in pups given continuous exposure to ethanol vapor. In Experiment 3, an ethanol pre-exposure phase (PD13) preceded tactile–ethanol pairings. During conditioning, pups were given distributed pairings between the tactile CS and ethanol or uncontaminated air. At test, ethanol-pre-exposed animals spent significantly more time on the ethanol-related CS than on an alternative texture. These results indicate that inhaled ethanol exerts differential hedonic effects in infant rats as a function of schedules of exposure that yield different levels of intoxication. Continuous experience with ethanol vapor induces aversive learning. Yet, pre-exposure to ethanol vapor allowed expression of ethanol-induced appetitive learning in pups given distributed vapor ethanol exposure.

Infant rats exhibit aversive learning mediated by ethanol's orosensory effects but are positively reinforced by ethanol's post-ingestive effects

Previous work suggest aversive and appetitive hedonic effects of intraorally delivered EtOH in pre-weanling rats. Pups are reluctant to perform an operant response when reinforced with intraoral EtOH infusions, a result suggesting aversive orosensory properties of EtOH. Yet, post-absorptive effects of ethanol seem capable of supporting appetitive conditioning. Two experiments were conducted to test this phenomenon. Both included a pre-exposure phase (postnatal day 13, PD13) comprising intraoral stimulation with water or EtOH. In Experiment 1, pups were given pairings between a tactile conditioned stimulus (CS) and intraoral infusions of EtOH or water. A subsequent tactile preference test revealed that pups spent significantly less on the EtOH-related CS relative to time spent on the alternative CS. In Experiment 2 pups were exposed to a texture CS (sandpaper) while intraorally infused with EtOH or during a later EtOH post-infusion interval. A tactile locational test conducted on PD16 indicated that EtOH-pre-exposed animals that experienced sandpaper paired with EtOH's post-absorptive effects exhibited a significant preference for the CS, even relative to a control group that experienced non-reinforced exposure to the tactile CS during conditioning. These results confirm that intraoral ethanol acts as an aversive tastant. A brief pre-exposure to EtOH allows later expression of appetitive learning mediated by the drug's post-ingestive effects.

Spatial location is critical for conditioning place preference with visual but not tactile stimuli.

The roles of visual, tactile, and spatial location cues were studied in 6 conditioned place preference (CPP) experiments with ethanol (2 g/kg) in mice (of the DBA/2J strain). Visual cues were effective conditioned stimuli (CSs) when consistently presented in the same spatial location, but not when the same cue was presented in two different locations during training. In contrast, tactile CSs were effective regardless of spatial location during training. Moreover, spatial location controlled CPP expression when visual cues were used but not when tactile cues were used. However, spatial location per se was not an effective CS. These studies suggest that CPP conditioned to tactile cues is mediated by brain systems different from those mediating CPP conditioned to visual-spatial cues.

Apparatus bias and the use of light and texture in place conditioning

In a typical conditioned place preference (CPP) preparation, animals alternately experience drug and vehicle effects in distinct chambers of an apparatus, spending more time in the drug-paired chamber post-conditioning. However, if all animals prefer the same chamber before conditioning, data interpretation may be compromised. Unbiased apparatus has been systematically validated with ethanol in mice ([Cunningham, C.L., Feree, N.K., Howard, M.A. Apparatus bias and place conditioning with ethanol in mice. Psychopharmacology (Berl) 2003;170:409–422]); the present study sought to identify and eliminate bias in a standard black-and-white apparatus and validate that apparatus for CPP with morphine and cocaine in rats. Apparatus bias was assessed in 24 adult female Sprague–Dawley rats. Subjects preferred the black chamber under bright lighting conditions, with no preference in the dark. Subjects then underwent a counterbalanced CPP regimen to 5 mg/kg SC morphine ( n = 12) or 20 mg/kg IP cocaine ( n = 12) using only tactile conditioned stimuli. Significant absolute preferences for the drug-paired chamber were produced by both drugs, with no effect of drug-paired chamber assignment on CPP expression; vehicle-treated controls ( n = 12) showed no preferences. Bias-free CPP to morphine and cocaine using standard apparatus in rats is possible. Implications for place conditioning are discussed, including the potential value of systematically exploiting apparatus bias in addition to eliminating it.

Origin, structure, and role of background EEG activity. Part 1. Analytic amplitude

Objective: To explain the neural mechanisms of spontaneous EEG by measuring the spatiotemporal patterns of synchrony among beta–gamma oscillations during perception. Methods: EEGs were measured from 8×8 (5.6×5.6 mm 2) arrays fixed on the surfaces of primary sensory areas in rabbits that were trained to discriminate visual, auditory or tactile conditioned stimuli (CSs) eliciting conditioned responses (CRs). EEG preprocessing was by (i) bandpass filtering to extract the beta-gamma range (deleting theta-alpha); (ii) low-pass spatial filtering (not high-pass Laplacians used for localization), (iii) spatial averaging (not time averaging used for evoked potentials), and (iv) close spacing of 64 electrodes for simultaneous recording in each area (not sampling single signals from several areas); (v) novel algorithms were devised to measure synchrony and spatial pattern stability by calculating variances among patterns in 64-space derived from the 8×8 arrays (not by fitting equivalent dipoles). These methodological differences are crucial for the proposed new perspective on EEG. Results: Spatial patterns of beta–gamma EEG emerged following sudden jumps in cortical activity called ‘state transitions’. Each transition began with an abrupt phase re-setting to a new value on every channel, followed sequentially by re-synchronization, spatial pattern stabilization, and a dramatic increase in pattern amplitude. State transitions recurred at varying intervals in the theta range. A novel parameter was devised to estimate the perceptual information in the beta-gamma EEG, which disclosed 2–4 patterns with high information content in the CS–CR interval on each trial; each began with a state transition and lasted ∼0.1 s. Conclusions: The function of each primary sensory neocortex was discontinuous; discrete spatial patterns occurred in frames like those in cinema. The frames before and after the CS–CR interval had low content. Significance: Derivation and interpretation of unit data in studies of perception might benefit from using multichannel EEG recordings to define distinctive epochs that are demarcated by state transitions of neocortical dynamics in the CS–CR intervals, particularly in consideration of the possibility that EEG may reveal recurring episodes of exchange and sharing of perceptual information among multiple sensory cortices. Simultaneously recorded, multichannel beta-gamma EEG might assist in the interpretation of images derived by fMRI, since high beta–gamma EEG amplitudes imply high rates of energy utilization. The spatial pattern intermittency provides a tag to distinguish gamma bursts from contaminating EMG activity in scalp recording in order to establish beta–gamma recording as a standard clinical tool. Finally, EEG cannot fail to have a major impact on brain theory.

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 [1]. 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 [2–4] and showed that a key modulatory neuron involved in the initiation of feeding ingestive movements [5] underwent a long-term depolarization following behavioral associative conditioning [6]. 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.

Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol Intoxication

Infant rats quickly learn to avoid a sensory cue paired with alcohol as an unconditioned stimulus, particularly when the drug reaches peak blood concentrations. In this study, a tactile cue paired with the onset of alcohol intoxication preceded subsequent presentations of a gustatory conditioned stimulus (CS). The goal was to address the possibility of differential conditioning depending on when stimuli were introduced during the course of the toxic state. In experiment 1, rat pups received sequential presentations of a salient texture (sandpaper) and a gustatory cue (saccharin) while intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture location tests and saccharin intake assessments were then performed. A third modality of assessment was defined by a saccharin intake test while pups simultaneously experienced sandpaper. In experiment 2, alcohol-mediated conditioning was followed by tests similar to those of experiment 1, but after pups were re-exposed to either the tactile CS or the alcohol-unconditioned stimulus. Conditioned taste aversions, due to pairing saccharin and the later stage of alcohol intoxication, were reliably established in both experiments. Also in both experiments, this excitatory aversive response was dramatically inhibited when the association between the texture CS and the earlier stage of alcohol intoxication was activated. There were no indications of conditioned motor responses to the tactile CS that might compete with intake behavior of saccharin or distort measurement of an appetitive memory derived from pairing the texture and the earlier stage of intoxication. Rat pups' expression of an association between a taste signaling aversive consequences of alcohol was eliminated by the presence of a tactile stimulus that originally had signaled the absence of aversive consequences of alcohol intoxication. The results suggest the interaction of inhibitory and excitatory conditioning involving the aversive properties of alcohol.

Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol Intoxication

Background: Infant rats quickly learn to avoid a sensory cue paired with alcohol as an unconditioned stimulus, particularly when the drug reaches peak blood concentrations. In this study, a tactile cue paired with the onset of alcohol intoxication preceded subsequent presentations of a gustatory conditioned stimulus (CS). The goal was to address the possibility of differential conditioning depending on when stimuli were introduced during the course of the toxic state. Methods: In experiment 1, rat pups received sequential presentations of a salient texture (sandpaper) and a gustatory cue (saccharin) while intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture location tests and saccharin intake assessments were then performed. A third modality of assessment was defined by a saccharin intake test while pups simultaneously experienced sandpaper. In experiment 2, alcohol-mediated conditioning was followed by tests similar to those of experiment 1, but after pups were re-exposed to either the tactile CS or the alcohol-unconditioned stimulus. Results: Conditioned taste aversions, due to pairing saccharin and the later stage of alcohol intoxication, were reliably established in both experiments. Also in both experiments, this excitatory aversive response was dramatically inhibited when the association between the texture CS and the earlier stage of alcohol intoxication was activated. There were no indications of conditioned motor responses to the tactile CS that might compete with intake behavior of saccharin or distort measurement of an appetitive memory derived from pairing the texture and the earlier stage of intoxication. Conclusions: Rat pups’ expression of an association between a taste signaling aversive consequences of alcohol was eliminated by the presence of a tactile stimulus that originally had signaled the absence of aversive consequences of alcohol intoxication. The results suggest the interaction of inhibitory and excitatory conditioning involving the aversive properties of alcohol.

Appetitive Learning Using Visual Conditioned Stimuli in the Pond Snail, Lymnaea

Feeding can be conditioned in the pond snail Lymnaea stagnalis to two different visual stimuli (a black panel or a 5-mm black and white check surround) by pairing the potential conditioned stimulus (CS) with sucrose. Exclusion of chemical cues (associated with differences between the water in home tank and that in training apparatus) that could serve as CS is important for successful visual conditioning. A featureless gray surround, used as an alternative to the check (to which it was matched in luminance) in counterbalanced training designs, was discriminated from the check, showing that resolution (for which the eyes would be necessary) was occurring. The gray surround was largely ineffective as a CS. Single-trial learning was possible with the black panel, but not with the check; it is argued that this may be due to lack of prior experience of stimuli like the check. Conditioning of feeding has now been obtained in Lymnaea to chemical, tactile, and visual cues, opening the way to comparative studies of the neural circuitry underlying appetitive conditioning in different senses, so far explored in Lymnaea only for tactile CS. Such comparative studies are as yet largely lacking in invertebrates.

Effects of stimulus modality and task condition on blink startle modification and on electrodermal responses

Participants in Experiments 1 and 2 performed a discrimination and counting task to assess the effect of lead stimulus modality on attentional modification of the acoustic startle reflex. Modality of the discrimination stimuli was changed across subjects. Electrodermal responses were larger during task-relevant stimuli than during task-irrelevant stimuli in all conditions. Larger blink magnitude facilitation was found during auditory and visual task-relevant stimuli, but not for tactile stimuli. Experiment 3 used acoustic, visual, and tactile conditioned stimuli (CSs) in differential conditioning with an aversive unconditioned stimulus (US). Startle magnitude facilitation and electrodermal responses were larger during a CS that preceded the US than during a CS that was presented alone regardless of lead stimulus modality. Although not unequivocal, the present data pose problems for attentional accounts of blink modification that emphasize the importance of lead stimulus modality.

Conditional discrimination learning in Aplysia californica

Two experiments examined whether the relation between a conditioned stimulus (CS) and an unconditioned stimulus (US) might be brought under the control of contextual stimuli in the invertebrate Aplysia californica. Subjects received exposure to 2 different contexts. In both experiments, a tactile CS was paired with a shock US in one of those contexts. In the other context, that tactile CS was either nonreinforced (Experiment 1) or explicitly unpaired with the shock US (Experiment 2). Responding to the CS during a subsequent test was greater in the context in which that CS had been paired with the US compared with the context in which it had been nonreinforced or unpaired. These findings are discussed in terms of theories of conditional discrimination learning.

The search for the psyche in drug dependence. A 35-year retrospective survey.

Thirty-five years ago, apparent interactions between intensities of morphine withdrawal phenomena in patients and presence or absence of the physician on the ward raised the question of the “organicity‘’ or “psychogenicity‘’ of the opioid abstinence syndrome. Operationally, “psychic‘’ was equated with “conditionable,‘’ requiring the integrity of the cerebral cortex, according to Pavlov. Evidence of tolerance to morphine and methadone and of severe abstinence syndromes was obtained in studies on long surviving deneocorticated dogs, chronic spinal dogs, and in a chronic spinal man. While the deneocorticated dogs could not acquire visual or auditory conditioned defense reflexes, surprisingly they did so with tactile conditioned stimuli after several hundred pairings of the tactile stimulus with the unconditioned stimulus, electric shock to a hindlimb, indicating the persistence of a rudimentary “psyche.‘’ However, in chronic spinal dogs, no conditioned reflex appeared after more than 1000 pairings of a tactile stimulus (applied to the tail) and electric shock to a hindlimb, evoking flexion. Hence, the opioid abstinence syndrome is organic, though that it may also become psychic given proper stimulus and reinforcement conditions, was not excluded. Indeed, anecdotal evidence of classical conditioning of the opioid abstinence syndrome and operant conditioning of opioid-seeking behavior was obtained in interviews with addicts and reports of other observers. Such conditioning could be an important factor in relapse long after opioid withdrawal when ex-addicts return to their drug-ridden home environment. In rats, a morphine abstinence sign, increased frequency of “wet dog shakes,‘’ could be classically conditioned to a specific environment and such conditioning persisted up to 155 days following permanent morhpine withdrawal. Also, ex-addict rats drank more of an opioid (etonitazene, 5μg/ml) than naïve rats in choice tests (etonitazene vs. water) at intervals for up to 1 year. That such “relapse‘’ may be due to conditioned reinforcing properties of etonitazene in rats that had previously undergone repeated cycles of morphine abstinence and its suppression was indicated in another study in which rats, while dependent on morphine, were repeatedly permitted to drink anise-flavored etonitazene which suppressed their morphine abstinence syndromes, while other morphine-dependent rats drank anise-flavored water. For 137 days following permanent morphine withdrawal, the previous anise-flavored etonitazene-drinking group drank more anise-flavored water than plain water compared to the other group or two groups of naïve rats treated similarly. Experimental extinction of such conditioned (psychic) responses may help prevent relapse of ex-addicts.

Decamethonium and the conditioned avoidance response.

The inhibition of performance of a conditioned avoidance response (CAR) by drugs has been a subject of much prominence in psychopharmacological research. This type of learned behavior is well known to be susceptible to selective suppression by diverse agents, especially the phenothiazine-type and reserpine-type tranquilizers, morphinelike analgesics, and centrally-acting cholinergic drugs (H~z, 1960). These agents and most others showing significant influence on CAR performance are accepted as acting via sites within the central nervous system (CNS). Utilizing the peripherally-acting agent tetraethylammonium, AvL~) (1950) found slower performance during both acquisition and extinction of a CAR which he attributed to the inhibition of ganglionic transmission. More recently, FS~LDMA~ (1960) has reported that well established CAR's of rats to either an auditory, visual or tactile conditioned stimulus (CS) were suppressed strikingly for short periods by some subparalytic action of a neuromuscular blocking agent, decamethoninm. He hypothesized that these changes might arise from an altered pattern of interoceptive sensory input to the CNS as a result of the muscle spindles (and in turn their proprioceptors) being affected by the subparalytic dosage of deeamethouium. In view of the paucity of data reported (two or three subjects per treatment group) and the novelty of this finding and the interpretation offered to explain it, we wished to attempt confirmation of the reported effect of decamethonium, and possibly to extend the study of its action. Materials and Methods Male albino rats (goltzman strain) were used at 120--150 days of age. Deeamethouium bromide (as Syncurine, Burroughs-Wellcome) was administered intraperitoneally in dosages of 0.4 and 0.8 mg/kg, the same as those utilized by FV~LD~A~r (1960). Drug or placebo treatment (0.9~ sahne) was administered to all rats 5 min before the test sessions. Loco

Afferent pathways of a tactile conditioned reflex after cortical somatosensory ablations

Abstract The retention of a tactile conditioned reflex after transection of two spinal pathways, separately or together, was studied in dogs with S I and S II previously removed uni- or bilaterally. Impairment of the reflex was observed in 1 3 cases after transection of the spinocervical tract but in no case after transection of the dorsal columns. Transection of the dorsal columns secondarily to a unilateral transection of the spinocervical tract, or vice versa, invariably caused major impairment of the reflexes from the side where both pathways were transected. It is concluded that the two pathways, exclusively of subserving rapid projection to S I and S II, may transmit activity elicited by the tactile conditioned stimulus to other central nervous structures of importance for the conditioned reflex. The results are discussed in relation to recent findings regarding thalamic connections of the two pathways.