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PubMed2000

Acute exposure to caffeine selectively disrupts context conditioning in rats.

RATIONALE AND OBJECTIVE: Acute caffeine administration has both beneficial and adverse effects on learning and memory; however, the brain regions underlying these effects remain unclear. Several experiments were conducted to examine the effects of acutely administered caffeine on the acquisition and expression of hippocampal-dependent and hippocampal-independent forms of conditioned fear. METHODS: In the first experiment, caffeine (10, 20, or 30 mg/kg; IP) or vehicle was administered to rats 15 min prior to classical fear conditioning, which consisted of ten tone-shock pairings. Freezing to the conditioning context was measured 24 h later, whereas tone-elicited fear was measured 48 h later. A second experiment examined possible state-dependent effects of caffeine by administering caffeine (30 mg/kg) or vehicle 15 min before conditioning and before testing. RESULTS: Pretreatment of acute caffeine severely impaired the acquisition of context conditioning, a hippocampal-dependent task. Tone conditioning, a hippocampal-independent task, was only modestly and non-significantly affected by caffeine (4-21% suppression compared with controls). The disruption of context conditioning was dose-dependent: 10 mg/kg had little effect on context or tone conditioning, whereas doses of 20 and 30 mg/kg caffeine severely disrupted context conditioning (73-87% suppression). In two subsequent experiments, it was found that caffeine's selective disruption of context conditioning could not be attributed to the fact that it is a weaker form of learning than tone conditioning or to state-dependent learning. CONCLUSIONS: Considered together, these results suggest that acute administration of caffeine may preferentially disrupt the acquisition of hippocampal-dependent learning, including context conditioning.

Animals↗

PubMed2001

The ventral hippocampus and fear conditioning in rats. Different anterograde amnesias of fear after tetrodotoxin inactivation and infusion of the GABA(A) agonist muscimol.

Studies on the involvement of the rat hippocampus in classical fear conditioning have focused mainly on the dorsal hippocampus and conditioning to a context. However, the ventral hippocampus has intimate connections with the amygdala and the nucleus accumbens, which are involved in classical fear conditioning to explicit and contextual cues. Consistently, a few recent lesion studies have indicated a role for the ventral hippocampus in classical fear conditioning to explicit and contextual cues. The present study examined whether neuronal activity within the ventral hippocampus is important for the formation of fear memory to explicit and contextual cues by classical fear conditioning. Tetrodotoxin (TTX; 10 ng/side), which completely blocks neuronal activity, or muscimol (1 microg/side), which increases GABA(A) receptor-mediated inhibition, were bilaterally infused into the ventral hippocampus of Wistar rats before the conditioning session of a classical fear-conditioning experiment. Conditioning to a tone and the context were assessed using freezing as a measure of conditioned fear. TTX blocked fear conditioning to both tone and context. Muscimol only blocked fear conditioning to the context. The data of the present study indicate that activity of neurons in the ventral hippocampus is necessary for the formation of fear memory to both explicit and contextual cues and that neurons in the ventral hippocampus that bear the GABA(A) receptor are important for the formation of fear conditioning to a context. In addition, both bilateral muscimol (0.5 microg/side and 1 microg/side) and TTX (5 ng/side and 10 ng/side) infusion into the ventral hippocampus dose-dependently decreased locomotor activity in an open-field experiment.

Acoustic Stimulation↗

PubMed1991

Separate controls for conditioned cephalic phases of acid secretion and drinking in the rat.

Adult male Sprague-Dawley rats, surgically equipped with a stainless steel gastric cannula, were tested in a paradigm known to support conditioning of cephalic phase gastric acid secretion. Rats were tested first under (a) baseline conditions--prepared to sham feed, but no food was offered and none should have been expected; then (b) 5 conditioning trials--prepared and allowed to sham feed sweetened milk; and finally (c) extinction trials--prepared to sham feed milk, but milk was not offered. Combined antagonism of H1 and H2 histamine receptors (using intraperitoneal dexbrompheniramine plus cimetidine) prevented the acquisition of conditioned cephalic phase of acid secretion, but had no effect on acquisition of conditioned water intake. Such histaminergic antagonism also blocked the expression of an established conditioned acid secretory response without effect on conditioned water intake; peripheral cholinergic blockade using atropine methyl nitrate had virtually the same effect as did histaminergic antagonism. The converse was observed following blockade of angiotensin II synthesis using subcutaneous captopril: Established conditioned secretion was unaffected, but conditioned water intake was inhibited. These results dissociate the physiological controls for conditioned responses which occur simultaneously in rats anticipating eating: Peripheral histamine mediates the acquisition and expression of the conditioned cephalic phase of acid secretion, whereas angiotensin II appears to mediate at least the expression of conditioned water intake.

Angiotensin II↗

PubMed2004

Maintenance of conditioned place preferences and aversion in C57BL6 mice: effects of repeated and drug state testing.

In order to determine the factors affecting the expression of place conditioning (i.e. conditioned place preference or aversion), groups of C57BL6 mice were conditioned to morphine, cocaine or naloxone (all drugs 4 mg/kg s.c.) and tested intermittently (up to 4 weeks) or repeatedly (daily). When tested once only in a drug-free state, the expression of place conditioning to all drugs generally strengthened with the passing of time and was only marginally different when tested once more later. The expression of place conditioning was remarkably resistant to extinction during repeated daily testing, though decreases were observed over 2 weeks of testing. Subsequently, a small and non-significant degree of spontaneous recovery of the expression of place conditioning was observed when animals were undisturbed for an extended period of time. Administering animals the same drug to which they were conditioned 20 min prior to testing (i.e. drug state testing), either prior to or following repeated testing, enhanced expression of morphine-induced conditioned place preference, whereas expression of cocaine-induced conditioned place preference was unaffected. When vehicle was administered prior to testing, there was no evidence of naloxone-induced conditioned place aversion, whereas naloxone administration maintained conditioned place aversion. These results show that the expression of place conditioning in C57BL6 mice does not readily diminish over time, but on the contrary, tends to strengthen if tested only once or intermittently. Thus, the hedonic properties of drugs may be more clearly revealed during long-term, rather than short-tem testing, and in some instances, when tested in the drugged state.

Anesthetics, Local↗

PubMed2006

Cholinergic modulation of trace conditioning trained in serial compound: A developmental analysis.

In four experiments the effects of serial compound conditioning on responding to a trace-conditioned CS were evaluated using a fear conditioning paradigm. The subjects were 18- and 25-day-old Sprague-Dawley rats, previously shown to exhibit little or no trace fear conditioning. Here, animals as young as 18 days of age were shown to be capable of trace conditioning between a visual CS1 and a shock US, provided the trace interval was filled with a non-target CS2 during serial conditioning trials (CS1-->CS2-->US). To explore cholinergic mechanisms involved in trace and serial conditioning, additional experiments assessed conditioned responding following pre-training administration of the muscarinic receptor antagonist scopolamine. Scopolamine produced a dose-dependent reduction in responding to the trace CS1, regardless of whether subjects were trained with standard trace (CS1-->trace interval-->US) or serial (CS1-->CS2-->US) trials. Responding to CS2 was unaffected by scopolamine. These data suggest that central cholinergic systems are functional in the young animals, but are not normally sufficiently activated by standard trace conditioning procedures. The results suggest that serial compound conditioning can promote trace conditioning in young rats, as it does in adults, perhaps by enhancing cholinergic activity during training. Implications for the late ontogenetic emergence of trace conditioning as it relates to maturation of neural pathways and their role in the potentiating effects of a gap filler are discussed.

Age Factors↗

PubMed2006

Cholinergic modulation of Pavlovian fear conditioning in rats: differential effects of intrahippocampal infusion of mecamylamine and methyllycaconitine.

The cholinergic system has consistently been implicated in Pavlovian fear conditioning. Considerable work has been done to localize specific nicotinic receptor subtypes in the hippocampus and determine their functional importance; however, the specific function of many of these subtypes has yet to be determined. An alpha7 nicotinic antagonist methyllycaconitine (MLA) (35 microg), and a broad spectrum non-alpha7 nicotinic antagonist mecamylamine (35 microg) was injected directly into the dorsal hippocampus or overlying cortex either 15 min pre-, 1 min post-, or 6h post-fear conditioning. One week after conditioning, retention of contextual and cue (tone) conditioning were assessed. A significant impairment in retention of contextual fear was observed when mecamylamine was injected 15 min pre- and 1 min post-conditioning. No significant impairment was observed when mecamylamine was injected 6h post-conditioning. Likewise, a significant impairment in retention of contextual fear was observed when MLA was injected 1 min post-conditioning; however, in contrast, MLA did not show any significant impairments when injected 15 min pre-conditioning, but did show a significant impairment when injected 6h post-conditioning. There were no significant impairments observed when either drug was injected into overlying cortex. No significant impairments were observed in cue conditioning for either drug. In general, specific temporal dynamics involved in nicotinic receptor function were found relative to time of receptor dysfunction. The results indicate that the greatest deficits in long-term retention (1 week) of contextual fear are produced by central infusion of MLA minutes to hours post-conditioning or mecamylamine within minutes of conditioning.

Aconitine↗

PubMed2003

Contribution of the anterior cingulate cortex to laser-pain conditioning in rats.

The emotional component of nociception is seldom distinguished from pain behavioral testing. The aim of the present study was to develop a behavioral test that indicates the emotional pain responses using the classical conditioning paradigm. The role of the anterior cingulate cortex (ACC) in the process of this pain conditioning response was also evaluated. In laser-pain conditioning, free moving rats were trained to associate a tone (conditioned stimulus, CS) and short CO(2) laser pulsation (unconditioned stimulus, US). Monotonous tone (800 Hz, 0.6 s) was delivered through a loud-speaker as CS. CO(2) laser pulses (5 W at 50 or 100 ms in duration) applied to the hind paw was adopted as US. The CS-US interval was 0.5 s. Laser-pain conditioning was developed during 40 CS-US pairings. CS and US pairing with 100-ms laser pulse stimuli was more effective in establishing conditioning responses than that of 50-ms stimuli. The conditioning responses remained, tested by presenting CS alone, immediate to and 24 h subsequent to training. The performance of laser-pain conditioning was significantly reduced after bilateral lesioning of the ACC. Similar results were also obtained by bilateral lesions of the amygdala. The conditioning responses were also diminished following morphine treatment. The association between a neutral stimulus and a noxious stimulus could be demonstrated in a Pavlovian conditioning test in free moving rats. Thus, the conditioned response may be employed as a measure of the emotional component of the nociception. It is also suggested that the ACC may play an important role in mediating this conditioning effect.

Acoustic Stimulation↗

PubMed1999

Effect of sex on fear conditioning is similar for context and discrete CS in Wistar, Lewis and Fischer rat strains.

Enhanced fear in males relative to females, both innate and conditioned, is a well-described characteristic of behavior in the laboratory rat. In the case of aversive conditioning to foot shock in Long-Evans rats, it has been described that conditioning to general (nondiscrete) contextual cues is greater in male rats relative to female rats, whereas conditioning to a discrete, predictive stimulis (CS) is not. These findings have been combined with evidence for greater levels of hippocampal LTP in males in Sprague-Dawley rats to derive a model of hippocampal-LTP-mediated contextual and not CS, fear conditioning. The present study reports on an analysis of the effect of sex in contextual and discrete CS conditioning to foot shock, assessed via measurement of freezing behavior in a novel automated paradigm, in three rat strains: Wistar, Fischer, and Lewis. In Wistar rats, there was a consistent but nonsignificant tendency for males to demonstrate both more contextual and more CS conditioning than females; in Fischer rats, males demonstrated both more contextual and more CS conditioning than females; in Lewis rats, a markedly enhanced acquisition of freezing in males did not translate into a sex difference in either context or CS conditioning at expression. Therefore, within each strain the effect of sex was consistent between context and CS conditioning. These findings, taken together with the hippocampal LTP evidence, suggest that the latter mediates both contextual and discrete CS aversive conditioning, and contributes to sex differences in both these forms of conditioning, in those strains where these sex differences exist.

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↗

PubMed1998

Lesion of the cerebellar interpositus nucleus or the red nucleus affects classically conditioned neuronal activity in the hippocampus.

1. The cerebellum and the hippocampus have been known to be neural structures involved in classical conditioning of the nictitating membrane response in rabbits. The neuronal activities related to conditioning are observed in both structures. It is uncertain, however, whether these conditioning-related neuronal activities are established in parallel or hierarchically. 2. The present study was conducted to observe the effects of lesions of the cerebellar interpositus nucleus(INT) or the red nucleus(RN) on conditioned hippocampal neuronal activity. 3. Rabbits in the first experiment were trained by standard delay conditioning and then given INT lesion by injecting the kainic acid through a cannula previously implanted. Lesions of INT abolished conditioned neuronal responses in the hippocampal CA1 area, which had been established before lesioning, as well as behavioral conditioned responses(CRs). 4. The second experiment was to examine if conditioning-related activities in the hippocampus would develop after RN was lesioned with INT intact. Rabbits were first given unilateral electrolytic lesions of RN followed by conditioning sessions. Besides a few CRs, they failed to show an increase in hippocampal CA1 activity. When training was switched to the contralateral eye, animals showed robust CRs and hippocampal responses immediately. However, training reswitched to the original eye, behavioral and neuronal responses disappeared again. 5. These results suggest that conditioned neuronal activities in the hippocampus depends on the cerebellum and that conditioning-related inputs from INT via RN may be critical for these conditioned neuronal response in the hippocampus.

Animals↗

PubMed1984

Effects of two antecedent conditions on vocalization frequency of severely retarded children.

Rather than concentrating exclusively on consequences in early vocal instruction, the manipulation of antecedent conditions has been recommended. Few empirical data have been collected on the effect of different antecedent events. Therefore, a series of three experiments was conducted with three severely retarded children to investigate the vocalization-producing potential of two antecedent conditions: adult talk, a commonly cited antecedent, and adult silence. The conditions were evaluated using a modified alternating treatments design. In Experiment 1, 5 min of continuous adult talk was alternated with 5 min of adult silence; the results indicated that adult silence occasioned more vocalizations than did adult talk. In Experiment 2, a mixed (alternating 30-s periods of silence and talk) condition was compared to a silence condition; again the results indicated a higher frequency of vocalization during the silence condition. In Experiment 3, a modified talk (a question or comment presented every 10 s) condition was compared to a silence condition; the results indicated that the two conditions occasioned similar vocalization frequencies for two children, and the questions/comments condition occasioned more vocalizations for one child. In addition to studying optimal conditions for adult talk, the present investigation provides a methodology for deriving empirical data on the effects of differing antecedent conditions on vocalization frequencies.

Child↗

PubMedDate not supplied

Pain report and pain-related evoked potentials operantly conditioned.

OBJECTIVE: The purpose of the present study was to answer the question whether pain report can be increased and decreased by operant conditioning. We predicted that the conditioned pain effects would remain significant after correction for social desirability and fantasy proneness. Furthermore, we tried to show that the neurophysiologic basis of verbal pain report, defined by pain (event)-related potentials, was affected by the conditioning procedure. Specifically, it was expected that the central recording site N150-P260 pain (event)-related potentials peak-to-peak amplitude would show the largest effect. METHODS: There were 4 groups: an up-conditioning group, a down-conditioning group, an at-random conditioning, and no-feedback control group. Healthy patients received 45 calibrated pain stimuli of equal physical intensity and were asked to rate the pain intensity they experienced. Up-conditioning was established by rewarding the subject if pain report increased compared with the previous trial. Down-conditioning of pain report was achieved by rewarding a decrease in the pain score. RESULTS: Results of the subjective pain reports clearly indicated that both forms of conditioning succeeded. Up-conditioning resulted in the highest pain scores and down-conditioning in the lowest scores with the two control groups in between them. Controlling for level of social desirability and fantasy proneness did not negatively influence these results. The N150-P260 pain (event)-related potentials peak-to-peak central recording site component also showed the predicted effect and reached statistical significance. DISCUSSION: We concluded that the subjective report of pain as well as a specific pain-related potentials component can be operantly conditioned.

Adolescent↗

PubMed2006

Theophylline inhibits tolerance and sensitization induced by morphine: a conditioned place preference paradigm study in female mice.

The effect of theophylline on reward properties of morphine was examined in the present study. A biased conditioned place preference paradigm was used to study the effects of theophylline on the development of conditioned place preference by morphine in sensitized and tolerant female mice. Subcutaneous injection of morphine (0.5-10 mg/kg) induced conditioned place preference in mice, while intraperitoneal administration of theophylline (2.5-100 mg/kg) did not induce conditioned place preference or conditioned place aversion. Theophylline (2.5-100 mg/kg) in combination with morphine (5 mg/kg), during conditioning sessions, decreased the acquisition of morphine conditioned place preference dose independently. Administration of theophylline (2.5-100 mg/kg) before testing also caused a significant reduction of the expression of morphine-induced conditioned place preference in a dose-independent manner. Administration of morphine (12.5, 25 or 50 mg/kg) daily, for 3 days, produced tolerance to conditioned place preference induced by the drug (5 mg/kg). Administration of theophylline (2.5 and 10 mg/kg) 1 h before morphine (12.5, 25 mg/kg), during development of tolerance, abolished morphine tolerance. A higher dose of theophylline (100 mg/kg), however, did not alter morphine tolerance. In addition, theophylline (2.5, 10 and 100 mg/kg) failed to reduce tolerance to a higher dose of morphine (50 mg/kg). Daily administration of morphine (5 mg/kg) for 3 days followed by a 5-day interval caused sensitization to morphine place conditioning. When theophylline was administered (2.5, 10 and 100 mg/kg) 1 h before morphine (5 mg/kg), during development of sensitization, inhibition of morphine-induced sensitization was demonstrated. The effect of theophylline was dose independent. It is concluded that while theophylline has no effect by itself, it reduced both the acquisition and expression of morphine conditioned place preference. In addition, theophylline reduced the acquisition of morphine conditioned place preference in morphine-sensitized and morphine-tolerant mice.

Animals↗

PubMedDate not supplied

Neural correlates of Pavlovian conditioning in components of the neural network supporting ciliary locomotion in Hermissenda.

Pavlovian conditioning in Hermissenda consists of pairing light, the conditioned stimulus (CS) with activation of statocyst hair cells, the unconditioned stimulus (US). Conditioning produces CS-elicited foot shortening and inhibition of light-elicited locomotion, the two conditioned responses (CRs). Conditioning correlates have been identified in the primary sensory neurons (photoreceptors) of the CS pathway, interneurons that receive monosynaptic input from identified photoreceptors, and putative pedal motor neurons. While cellular mechanisms of acquisition produced by the synaptic interaction between the CS and US pathways are well-documented, little is known about the mechanisms responsible for the generation or expression of the CR. Here we show that in conditioned animals light reduced tonic firing of ciliary activating pedal neurons (VP1) below their pre-CS baseline levels. In contrast, pseudorandom controls expressed a significant increase in CS-elicited tonic firing of VP1 as compared to pre-CS baseline activity. Identified interneurons in the visual pathway that have established polysynaptic connections with VP1 were examined in conditioned animals and pseudorandom controls. Depolarization of identified type Ie interneurons with extrinsic current elicited a significant increase in IPSPs recorded in VP1 pedal neurons of conditioned animals as compared with pseudorandom controls. Conditioning also enhanced intrinsic excitability of type Ie interneurons of conditioned animals as compared to pseudorandom controls. Light evoked a modest increase in IPSP frequency in VP1 of conditioned preparations and a significant decrease in IPSP frequency in VP1 of pseudorandom controls. Our results show that a combination of synaptic facilitation and intrinsic enhanced excitability in identified components of the CS pathway may explain light-elicited inhibition of locomotion in conditioned animals.

Animals↗

PubMed2006

Selective excitotoxic lesions of the hippocampus and basolateral amygdala have dissociable effects on appetitive cue and place conditioning based on path integration in a novel Y-maze procedure.

The hippocampus and amygdala are thought to be functionally distinct components of different learning and memory systems. This functional dissociation has been particularly apparent in pavlovian fear conditioning, where the integrity of the hippocampus is necessary for contextual conditioning, and of the amygdala for discrete cue conditioning. Their respective roles in appetitive conditioning, however, remain equivocal mainly due to the lack of agreement concerning the operational definition of a 'context'. The present study used a novel procedure to measure appetitive conditioning to spatial context or to a discrete cue. Following selective excitotoxic lesions of the hippocampus (HPC) or basolateral amygdala (BLA), rats were initially trained to acquire discrete CS-sucrose conditioning in a Y-maze apparatus with three topographically identical chambers, the chambers discriminated only on the basis of path integration. The same group of animals then underwent 'place/contextual conditioning' where the CS presented in a chamber assigned as the positive chamber was paired with sucrose, but the same CS presented in either of the other two chambers was not. Thus, spatial context was the only cue that the animal could use to retrieve the value of the CS. HPC lesions impaired the acquisition of conditioned place preference but facilitated the acquisition of cue conditioning, while BLA lesions had the opposite effect, retarding the acquisition of cue conditioning but leaving the acquisition of conditioned place preference intact. Here we provide strong support for the notion that the HPC and BLA subserve complementary and competing roles in appetitive cue and contextual conditioning.

Amygdala↗

PubMed1988

Baroreflex unimpaired by operant avoidance or classical aversive conditioning in dogs.

Previous studies showed that baroreflex control of heart rate is impaired during operant shock avoidance conditioning and classical aversive conditioning. However, the effects of such "emotionally stressful" paradigms on the ability of the baroreflex to control arterial pressure have not been directly assessed. We prepared the carotid sinus regions of dogs for reversible isolation from the systemic circulation, and we derived complete stimulus-response relations for the effects of carotid sinus pressure on both heart rate and arterial pressure. For any given carotid sinus pressure, arterial pressure and heart rate were higher during operant shock-avoidance conditioning and during classical aversive conditioning than in a neutral environment, which indicates an upward resetting of the baroreflex. However, threshold and saturation carotid sinus pressures were unaffected by operant conditioning or classical conditioning, which indicates that the baroreceptors themselves were not reset. The ranges over which the carotid baroreflex could vary arterial pressure and heart rate were significantly increased during both operant conditioning and classical conditioning. Baroreflex gain was unchanged during operant conditioning and was significantly increased during classical conditioning. We conclude that the baroreflex is not impaired during operant shock-avoidance conditioning or classical aversive conditioning in dogs. However, the baroreflex is reset and regulates blood pressure at an elevated level.

Animals↗

PubMed2006

H-reflex operant conditioning in mice.

Rats, monkeys, and humans can alter the size of their spinal stretch reflex and its electrically induced analog, the H-reflex (HR), when exposed to an operant conditioning paradigm. Because this conditioning induces plasticity in the spinal cord, it offers a unique opportunity to identify the neuronal sites and mechanisms that underlie a well-defined change in a simple behavior. To facilitate these studies, we developed an HR operant conditioning protocol in mice, which are better suited to genetic manipulation and electrophysiological spinal cord study in vitro than rats or primates. Eleven mice under deep surgical anesthesia were implanted with tibial nerve stimulating electrodes and soleus and gastrocnemius intramuscular electrodes for recording ongoing and stimulus-evoked EMG activity. During the 24-h/day computer-controlled experiment, mice received a liquid reward for either increasing (up-conditioning) or decreasing (down-conditioning) HR amplitude while maintaining target levels of ongoing EMG and directly evoked EMG (M-responses). After 3-7 wk of conditioning, the HR amplitude was 133 +/- 7% (SE) of control for up-conditioning and 71 +/- 8% of control for down-conditioning. HR conditioning was successful (i.e., > or =20% change in HR amplitude in the appropriate direction) in five of six up-conditioned animals (mean final HR amplitude = 139 +/- 5% of control HR for successful mice) and in four of five down-conditioned animals (mean final HR amplitude = 63 +/- 8% of control HR for successful mice). These effects were not attributable to differences in the net level of motoneuron pool excitation, stimulation strength, or distribution of HR trials throughout the day. Thus mice exhibit HR operant conditioning comparable with that observed in rats and monkeys.

Afferent Pathways↗

PubMed1989

Classical conditioning reduces amplitude and duration of calcium-dependent afterhyperpolarization in rabbit hippocampal pyramidal cells.

1. The afterhyperpolarization (AHP) that follows action potentials was studied in CA1 hippocampal pyramidal cells from classically conditioned and control rabbits. Measurements of the AHP were obtained with intracellular recordings from CA1 cells within hippocampal slices. 2. The AHP of rabbit CA1 pyramidal cells was found to be accompanied by a conductance increase. The AHP was reduced by bath applications of the calcium channel blockers, cadmium and cobalt, by bath application of the cholinergic agonist, carbamylcholine chloride, and intracellular injection of the calcium chelator, ethylene glycol-bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). 3. The AHP was markedly reduced in cells from rabbits that were well-trained with the nictitating membrane conditioning procedure, as compared with cells from pseudoconditioned or naive control animals. The difference in AHP amplitudes between conditioned and control groups increased as the number of spikes elicited by the stimulation pulse increased from one to four. Both the duration (measured as the time constant of AHP decay) and amplitude of the AHP were reduced in cells from conditioned animals. 4. The reduced AHP in cells from conditioned animals remained reduced in a medium that contained 0.5 microM tetrodotoxin (TTX) and 5.0 mM tetraethylammonium chloride (TEA); the AHP following calcium spikes was measured under these conditions. Since this medium eliminated synaptic transmission elicited by Schaeffer collateral stimulation, the AHP reduction in pyramidal cells from conditioned animals was not due to a modification in synaptic properties. There were no significant differences in the mean voltage thresholds, amplitudes, or durations of calcium spikes between cells from animals in the three groups. Thus the AHP reduction appears to be due to a modification of a Ca2+ -dependent K+ conductance and was not due to a secondary effect of reductions in calcium conductances underlying the spike. 5. In medium containing TTX and TEA, the amount of injected current required to elicit a calcium spike (current threshold) was significantly greater in cells from conditioned animals than in cells from control animals. This increase in current threshold persisted in 4-aminopyridine (4-AP)-containing medium and so cannot be attributed entirely to conditioning-specific increases in the A-current. 6. The conditioning-specific AHP reduction resulted in increased excitability in cells from conditioned animals versus pseudoconditioned control animals. Cells from conditioned animals fired more spikes to trains of 100-ms depolarizing current pulses than did cells from controls.

4-Aminopyridine↗