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PubMed1996

Increased firing of neurons in the posterior hypothalamus which precede classically conditioned pupillary dilations.

Paralyzed cats were used as subjects in a classical conditioning experiment where each subject was exposed to 40 explicitly unpaired 1-s bursts of white noise and 0.5-s paw shocks. This training was followed by 60 trials of the two stimuli paired, where the white noise immediately preceded the paw shock. Following this training, the subjects were re-exposed to 40 trials of the explicitly unpaired procedure. The pupil was monitored as the behavior and electrodes implanted in the thalamus, the dorsal hypothalamus and the posterior hypothalamus recorded the activity of clusters of cells. Only the cells in the posterior hypothalamus showed robust changes in firing rates that preceded the pupillary behavior, both (a) on any particular trial and (b) as the learned association was being demonstrated behaviorally across trials.

Animals↗
PubMed1999

GABA immunoreactivity in mouse barrel field after aversive and appetitive classical conditioning training involving facial vibrissae.

We have previously reported that a classical conditioning paradigm involving stimulation of a row of facial vibrissae produced an expansion of the cortical representation of the "trained row", labeled with 2-deoxyglucose (2DG), in layer IV of the barrel field. The present study has examined the pattern of GABA immunoreactivity (GABA-IR) in the cortical representation of row B of the facial vibrissae after (i) 3 days of aversive training, and (ii) 2 months of appetitive training, where stimulation of row B of vibrissae on one side of the snout was used as a conditioned stimulus. The most notable observation was a greater density of GABA-IR cells concentrated in the hollows of the "trained row" B barrels compared to the hollows in the barrel field of the opposite hemisphere in the same mouse. After aversive training, we noted a 2-fold increase in the density of GABA-IR neurons in the hollows of row B; after reward training, the increase amounted to 49%. In contrast, GABA-IR was unchanged in the control groups, which received only stimulation of vibrissae without the unconditioned stimulus. The classification of labeled neurons according to size revealed that the increase in density of GABA-IR neurons was confined to the small (12-15 microm) diameter group. We concluded that the GABAergic system undergoes up-regulation, after both associative learning paradigms, and that the population of small, GABAergic neurons plays an active role in use-dependent plasticity.

Animals↗
PubMed1999

Classical conditioning during nitrous oxide treatment: influence of varying the interstimulus interval.

Classical conditioning of the rabbit nictitating membrane response (NMR) was accomplished by presenting a 75-ms tone conditioned stimulus (CS) at intervals of 0, 100, 200, 400, and 800 ms before the presentation of a 100-ms shock unconditioned stimulus. Following every four paired trials (tone followed by shock), the occurrence of conditioned responses (CRs) was tested on every fifth trial in which only tone was presented (test trials). Three doses of nitrous oxide in oxygen (0, 33, and 67%) were used during conditioning. Nitrous oxide produced dose-dependent decrements of learning. Conditioned responding was related to the interstimulus interval (ISI) by a concave-down function. The higher dose of nitrous oxide caused more decrements of learning at several ISIs compared to the other two doses, changing the shape of the curve. Trace conditioning, which was examined in the present study, was more impaired under the influence of nitrous oxide than conditioning in a previous study, which used the standard delay paradigm. Thus, the drug impairs explicit memory more than implicit memory.

Acoustic Stimulation↗
PubMed1962

Classical conditioning in newborn rats.

Newborn albino rats were trained according to classical conditioning procedure wih one of four intervals between conditioned and unconditioned stimuli. A vibrotactile stimulus (conditioned stimulus) paired with an electric shock (unconditioned stimulus) was presented to the forelimb 80 times. The results demonstrate that conditioning takes place in newborn rats. However, levels of performance as a function of time intervals between stimuli did not resemble the levels traditionally reported for older animals.

Animals↗
PubMed2000

Impairment in eyeblink classical conditioning in adult rats exposed to ethanol as neonates.

BACKGROUND: Eyeblink classical conditioning is a learning task that engages well-defined neural circuitry in the cerebellum and brainstem. Binge-like exposure to alcohol during the neonatal brain growth spurt in rats produces neurotoxic effects on both the cerebellum and the brainstem. The precise localization of the neural substrates of eyeblink conditioning makes it an ideal task to study functional disruptions in the cerebellum and brainstem caused by early exposure to alcohol. The purpose of this study was to determine whether impairments in eyeblink conditioning caused by neonatal binge exposure to alcohol persist into adulthood, indicative of long-lasting abnormalities in cerebellar and brainstem function. METHODS: Group Ethanol received alcohol doses of 5.25 g/kg/day via intragastric intubation on postnatal days 4-9. Group Sham Intubated underwent the intragastric intubation procedures on postnatal days 4-9 but did not receive any infusions. Group Nonintubated did not receive any intubations. When all rats were at least 3 months old, they were tested in either paired or unpaired eyeblink conditioning. RESULTS: Group Ethanol showed impaired eyeblink conditioning and some abnormalities in conditioned response timing. Control groups did not differ from each other. CONCLUSIONS: The present data indicate that early exposure to alcohol has long-term effects on eyeblink conditioning, perhaps through enduring effects associated with alcohol-induced loss of Purkinje cells of the cerebellum.

Animals↗
PubMed1993

Differential expression of correlates of classical conditioning in identified medial and lateral type A photoreceptors of Hermissenda.

Classical conditioning of Hermissenda produces neurophysiological correlates in the primary sensory neurons of the pathway mediating the conditioned stimulus (CS), the type B and type A photoreceptors. Biophysical and biochemical changes intrinsic to the type B photoreceptors have been studied extensively in conditioned animals. A second site for intrinsic modification with learning has been recently identified in type A photoreceptors. We have recorded from identified medial and lateral type A photoreceptors in conditioned animals and animals that received pseudorandom presentations of light (CS) and rotation (unconditioned stimulus). Here we report that conditioning produces differential effects upon CS-elicited spike frequency and intrinsic excitability detected in identified lateral and medial type A photoreceptors. Lateral type A photoreceptors from conditioned animals exhibited significant increases in spike frequency elicited by the CS as compared to pseudorandom controls. In contrast, CS-elicited spike frequency recorded in medial type A photoreceptors was not significantly different from random controls. The amplitude of the peak and plateau phases of the generator potential of medial and lateral type A photoreceptors was decreased in conditioned animals as compared to random controls. In addition, only lateral type A photoreceptors exhibited enhanced cellular excitability as expressed by increased spike discharges produced by the injection of extrinsic depolarizing current pulses. Conditioning also decreased spike frequency accommodation in lateral type A photoreceptors. In normal controls, medial type B photoreceptors produced stronger synaptic inhibition of medial type A photoreceptors than the lateral type B photoreceptors inhibition of lateral type A photoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Summation of baroreflex and classically conditioned heart rate responses in dogs.

Following instrumentation with pneumatic cuffs around the inferior vena cava and the descending aorta, dogs were studied either following differential classical conditioning or in a control state. The cuffs functioned to raise and lower blood pressure for the construction of baroreflex curves for heart rate. Conditioned dogs received 8 trials each day with each CS+ (tone paired with flank shock) and CS- (a different tone without shock). Curves were constructed from cuff inflations timed to coincide with the maximum conditioned heart rate response. These curves were constructed from data acquired during infusion of saline, methyl atropine, or propranolol. Comparison of these curves revealed that the CS+ shifted the curves toward higher heart rates while the CS- curve was shifted toward lower heart rates without a change in gain. The amount of shift was comparable to that of the conditioned heart rate response. This suggested that the responses were independent and additive. Neither propranolol nor atropine eliminated this separation between the curves induced by the conditioning. These observations lead us to conclude that classically conditioned stress and baroreceptor stimulation exert independent control over heart rate that are mediated by both sympathetic and parasympathetic influences.

Animals↗
PubMed1975

Classical conditioning of autonomic responses in alert and drowsy subjects.

The primary purpose of this experiment was to study classically conditioned autonomic responses of alert versus drowsy subjects. Sixty-nine subjects in conditioning and pseudo-conditioning groups were subdivided into alert and drowsy groups on the basis of EEG recordings during conditioning trials, giving a total of four groups: conditioning-alert, conditioning-drowsy, pseudoconditioning-alert and pseudoconditioning-drowsy. Using the latency criterion to define responses, significant conditioning occurred only in the conditioning-alert group for the following measures: skin resistance anticipatory and UCS-omission responses, and finger plethysmograph anticipatory response. Both conditioning groups showed evidence of conditioned UCS-omission plethysmograph responses. Discussion centered primarily on (1) the implications of the results on the question of the feasibility of learning during sleep; and (2) the importance of including EEG recordings in studies of classically conditioned autonomic responses. The relationship between the various responses was also evaluated.

Acoustic Stimulation↗
PubMed1976

Orienting and classical conditioning in the rabbit (Oryctolagus cuniculus): effects of septal area lesions.

Rabbits with either sham or septal lesions recieved differential classical conditioning training in which tones of different frequencies served as CSs and paraorbital shock served as the UCS. Eyeblink (EB), EMG, and heart rate (HR) CRs were concommitantly assessed. Free field activity was also studied in selected animals. Animals with septal lesions revealed an impaired EB discrimination which resulted from increased responding to the CS-. These animals showed HR CRs of greater magnitude than sham animals. The HR discrimination was, however, unimpaired by septal lesions. Differential EMG activity also occurred, but was unaffected by septal destruction. Septal lesions resulted in greater free-field activity associated with visual stimulation, but no differences were obtained between septal and sham animals in the dark. It is suggested that these results were due to an enhanced reactivity to environmental stimulation, possibly related to dysfunctions of the orienting reflex.

Animals↗
PubMed1999

Classical conditioning of the electrically elicited blink reflex in humans: a new method of data analysis.

The eyeblink conditioning paradigm is a well-established model to study learning processes in humans and animals. Especially results from animal studies have supplied new insight into physiological pathways and brain structures involved in associative motor learning and memory. An important role of the cerebellum and its afferent fiber systems could be shown. Recent studies in humans have given evidence that results of animal experiments can be applied directly to the human condition. A high variation of baseline EMG activity and/or spontaneous blinks may influence the analysis of classical conditioning of the electrically elicited blink reflex in humans. To optimize differentiation between real conditioned responses and stimulus-independent EMG activity, we developed an algorithm which is fully automated and independent of a possible bias of an examiner. In a first step the algorithm decides whether a subject fulfills the criteria of a successful learning process or not. The second step quantifies the learning process. For quantification of the learning process, the following parameters were calculated: number of conditioned responses, onset of conditioning, time and amount of maximal conditioning, speed of conditioning and speed of habituation. According to our criteria, 80% of the healthy volunteers acquired conditioned responses. There is an age-related decline in eyeblink classical conditioning. Analysis of patient groups with different types of lesions will further improve our knowledge and understanding of pathways involved in learning processes in humans. The proposed new algorithm of data analysis takes less than 10 s on a standard computer, is more sensitive and more specific in detecting conditioned responses and, therefore, may further improve the value and reliability of the eyeblink conditioning paradigm in clinical research.

Adult↗
PubMed1983

Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response.

Through the use of a chronic microdrive recording system, neuronal unit activity was recorded throughout the brainstem of the rabbit during performance of the classically conditioned nictitating membrane (NM) extension/eyeblink response using an acoustical conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS). Regions which exhibited neuronal responses near the onset of the learned response were found to be relatively localized to: the abducens, accessory abducens, and facial nuclei (the motoneurons known to innervate the muscles responsible for expression of the conditioned response); the sensory nuclei of the fifth (probably representing somatosensory or proprioceptive feedback from the conditioned response); the superior colliculus; the periaqueductal gray; various reticular regions and the brainstem nuclei directly connected with the cerebellum (pontine nuclei, tegmental reticular nucleus (Bechterew), red nucleus, and perhaps the inferior olive). Stimulus (tone-airpuff) evoked responses were found within all classical auditory nuclei of the brainstem; the superior colliculus; the periaqueductal gray; pontine nuclei; fifth sensory nuclei, and various reticular regions. Recent lesion studies have shown the ipsilateral cerebellum to be essential for the learning and retention of this response. Collectively these results indicate that the cerebellum and its related brainstem nuclei are critically involved in the control and production of the classically conditioned NM/eyeblink response and may contain essential long term neuronal changes--the 'memory trace'--which serves to encode this learned response.

Acoustic Stimulation↗
PubMed2006

Effects of 4-aminopyridine on classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response.

A large body of data suggests that potassium channels may play an important role in learning and memory. Previous in-vitro research in a number of species including Hermissenda and the rabbit suggests that a 4-aminopyridine-sensitive transient potassium channel may be involved in classical conditioning. We investigated the effects of in-vivo 4-aminopyridine administration (0.5 mg/kg) on classical conditioning of the rabbit nictitating membrane response using a battery of tests designed to assess the associative, sensory, and motor contributors of 4-aminopyridine to responding. 4-Aminopyridine enhanced both classical conditioning and conditioning-specific reflex modification compared with a saline vehicle control, and these effects had several nonassociative components including an increase in the frequency of responding to both the conditioned and the unconditioned stimuli, suggesting a sensitizing effect of the drug. Although 4-aminopyridine can have peripheral effects, it may also modify cerebellar excitability or hippocampal neurotransmitter balance resulting in heightened responsiveness to stimulation.

4-Aminopyridine↗
PubMed2004

Distribution of anterogradely labeled trigeminal and auditory nerve boutons on abducens motor neurons in turtles: implications for in vitro classical conditioning.

A conditioned abducens nerve response is generated in in vitro brainstem preparations from turtles by pairing a weak conditioned stimulus (CS) applied to the auditory nerve that immediately precedes an unconditioned stimulus (US) applied to the trigeminal nerve. Tract-tracing studies showed direct projections from auditory and trigeminal nerves to abducens motor neurons. In light of these findings for convergent CS-US inputs, it is hypothesized that auditory and trigeminal nerve synaptic inputs onto abducens motor neurons are in spatial proximity because the CS is a weak input that may be required to be near the US inputs to have an associative effect, and conditioning occurs only when the CS and US are temporally separated by less than 100 ms. This study examined the spatial relationship of 133 anterogradely labeled synaptic boutons conveying CS or US information on retrogradely labeled abducens motor neurons. The results show that trigeminal and auditory nerve terminal fields occupy primarily the soma and proximal dendrites of abducens motor neurons. Quantitative analysis shows that the majority of labeled boutons (76% and 85% from injections of the trigeminal and auditory nerves, respectively) were apposed to somata or were localized to dendritic segments no more than about 30 microm from the nucleus. There were no quantitative differences between trigeminal and auditory nerve boutons in terms of their localization on dendrites or bouton diameter. Finally, triple labeling experiments demonstrated that individual abducens motor neurons receive inputs from both nerves and that these inputs may be in close spatial proximity to one another. This synaptic arrangement allows for the possibility that in vitro abducens conditioning is generated by coincident CS-US detection mediated by NMDA receptors and may utilize a Hebbian-like plasticity mechanism.

Abducens Nerve↗
PubMed1980

Acquisition and retention of classical conditioning in the newborn rat.

The development of memory of a conditioned response was examined in London black rats between 0 and 4 days of age. For the conditioning, a vibrotactile stimulus paired with an electric shock was presented to the animal 80 times with an interval of 2000 msec between stimuli. The animals were retested at retention intervals of 3 min or 24 hr. The results showed that 0-, 2-, 3-, and 4-day-old rats possess a retention capacity of at least 24 hr and suggest that the emergence of memory may be task-specific.

Animals↗
PubMed1988

Reinforcers in infancy: classical conditioning using stroking or intra-oral infusions of milk as UCS.

Six-day-old rats received 20 forward pairings of an odor-conditioned stimulus (CS) with one of two unconditioned stimuli (UCS); 1) intra-oral milk infusions or 2) stroking with a sable-hair brush. These UCS's produce a common general response of increased behavioral activity, but different specific behaviors. For each UCS, additional pups received backward pairings of the CS and UCS, random pairings of the CS and UCS, CS only, UCS only, or no stimuli. Four hours later, pups received a two-odor choice test to assess the development of an odor preference and a CS-only test to assess the acquisition of conditioned responding (CR). The results of the two-odor choice test indicated that for both UCS's only forward pairings of the CS and UCS resulted in an odor preference. Similarly, the CS-only test showed that only forward pairings of the CS and either UCS were effective in producing CR's; pups that received forward pairings exhibited increased behavioral activity during presentations of the CS, which is an unconditioned response (UCR) to both UCS's. Only the forward paired CS-milk UCS group exhibited increased mouthing and probing during the CS only test; these are UCR's that occur to milk infusions but infrequently to the stroking UCS. These results demonstrate the development of similar conditioned odor preferences using behaviorally activating UCS's, but CR's which are specific to the form of the UCR.

Animals↗
PubMed1988

Behavioral and physiological detection of classically-conditioned blood pressure reduction.

Spontaneously hypertensive (SH) rats were trained to discriminate the effects of saline injection from the interoceptive stimuli associated with the blood-pressure-reducing effect of clonidine (0.02 mg/kg, IP) in a drug discrimination procedure. Anise/ethanol and ethanol odors were then systematically paired with clonidine and saline treatment, respectively, outside the drug discrimination setting. As the number of pairings increased, the anise/ethanol (but not the ethanol) stimulus, when given alone, came to both reduce blood pressure and to mimic clonidine's interoceptive stimulus to virtually the same extent as clonidine itself. Both responses induced by the conditioned stimulus (CS+; anise/ethanol odor) were antagonized by the noradrenergic alpha-2 receptor antagonist yohimbine at a dose that did not by itself influence blood pressure. These data support the hypothesis that activation of endogenous factors can be elicited by a CS, and that these factors may furthermore act agonistically at central alpha-2 receptors to reduce blood pressure in hypertensive animals.

Animals↗
PubMed1985

Mental rehearsal and classical conditioning contribute to ethanol tolerance in humans.

Four groups of six male social drinkers learned a motor skill task and then drank the same dose of ethanol (0.62 g/kg) during each of five drinking sessions. Sessions 1 and 5 provided pre- and posttreatment measures of ethanol effects on task performance. During treatment sessions 2 to 4, two groups mentally rehearsed (MR) the task after drinking, either in the same test environment (MRSE) or in an entirely different environment resembling a library (MRDE). The other two groups received no MR after consuming ethanol, and simply performed an auditory detection task, either in the same test room (NMRSE) or in the different room (NMRDE). Posttreatment impairment of task performance under ethanol revealed significant main effects of mental rehearsal (P = 0.04) and environment (P = 0.04). The MRSE group was least impaired (i.e., most tolerant), and the NMRDE group was most impaired. Thus, repeated mental rehearsal and repeated exposure to the same test environment under ethanol each facilitated behavioral tolerance to ethanol.

Adult↗