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PubMed1975

Stimulus compounding in classical fear conditioning.

The effect of stimulus compounding in classical conditioning was investigated by conditioning one group of rats to a compound CS consisting of a buzzer and light and then conditioning separate groups of rats to the individual elements of the compound CS. On hurdle-jump test trials, the group of Ss conditioned to the compound CS performed better than Ss conditioned to the elements of the compound. Strength of conditioning to each of the elements of the compound CS was about equal. There was some evidence of a summation effect resulting from conditioning to the compound CS. Strength of conditioning to the compound CS was somewhat greater than the sum of the response strengths conditioned to the elements of the compound CS.

Acoustic Stimulation↗
PubMed1996

Facilitation and retardation of flavour aversion conditioning following prior exposure to the CS.

Two sets of experiments on flavour aversion conditioning in rats examined the effects of the following factors: the nature of the flavour serving as the conditioned stimulus (CS), which was either a compound of monsodium glutamate, sucrose and quinine, or an elemental flavour, either sucrose or dilute acid; the amount of the CS rats consumed on a single conditioning trial-4 ml or 1 ml; and whether rats had been pre-exposed to the CS before this conditioning trial. There were three main findings. First, conditioning to an elemental CS was unaffected by the amount consumed on the conditioning trial, but conditioning to 1 ml of the compound CS was poorer than to 4 ml. Second, pre-exposure produced a latent inhibition effect if the CS was an elemental flavour, or if rats were allowed to drink 4 ml of the compound solution on their conditioning trial. But, third, pre-exposure facilitated conditioning in rats given only 1 ml of the compound solution as their CS.

Animals↗
PubMed1996

The topography of sexually conditioned behaviour: effects of a trace interval.

In a trace conditioning procedure, subjects were presented with a 30-sec conditioned stimulus (CS) followed by a 30-sec trace interval. Delayed conditioning consisted of a 60-sec CS presentation followed by an unconditioned stimulus (US). Although conditioning developed with both procedures, the topography of the conditioned response differed. Sexual conditioned approach was evident in all of the subjects during the presentation of the CS. Trace-conditioned subjects moved away from the area where the CS had been presented during the trace interval but remained closer to the CS location than did an unpaired control. This reduction in the spatial specificity of the conditioned response was interpreted from a behaviour systems perspective. The trace interval presumably increased the perceived separation between the CS and the US and therefore elicited conditioned behaviour less specifically directed towards the CS.

Animals↗
PubMed1998

Anti-Gal(alpha)1-3Gal antibody response to porcine bone marrow in unmodified baboons and baboons conditioned for tolerance induction.

BACKGROUND: Mixed lymphohematopoietic chimerism can provide an effective means of inducing longterm immunological tolerance and has been documented in a monkey allograft model. A conditioning regimen including nonmyeloablative or myeloablative irradiation and splenectomy has been used to induce chimerism in a pig-to-primate transplantation model. Since the presence of anti-Gal(alpha)1-3Gal (alphaGal) natural antibodies leads to the hyperacute rejection of pig organs transplanted into primates, extracorporeal immunoaffinity adsorption (EIA) of anti-alphaGal antibodies is also included in the regimen. The effect of the tolerance induction protocol on the anti-alphaGal antibody response has been assessed. METHODS: Anti-alphaGal antibody was measured after the EIA of plasma through an alphaGal immunoaffinity column in baseline studies involving two unmodified baboons, one splenectomized baboon, and one baboon that received a challenge with porcine bone marrow (BM), and in three groups of baboons (n=2 in each group) that received different conditioning regimens for tolerance induction. Group 1 received a nonmyeloablative conditioning regimen without porcine BM transplantation. Group 2 received nonmyeloablative conditioning with pig BM transplantation and pig cytokine therapy. Group 3 received myeloablative conditioning, an autologous BM transplant (with BM depleted of CD2+ or CD2+/CD20+ cells), and pig BM transplantation. RESULTS: In the baseline studies, a single EIA of anti-alphaGal antibodies in an unmodified animal initially depleted anti-alphaGal antibody, followed by a mild rebound. Nonmyeloablative conditioning (group 1) in the absence of pig cell exposure reduced the rate of anti-alphaGal antibody return. Pig BM cells markedly stimulated anti-alphaGal antibody production in an unmodified baboon (alphaGal IgM and IgG levels increased 40- and 220-fold, respectively). This response was significantly reduced (to an only 2- to 5.5-fold increase of IgM and IgG) in baboons undergoing nonmyeloablative conditioning (group 2). A myeloablative conditioning regimen (group 3) prevented the antibody response to pig BM, with the reduction in response being greater in the baboon that received autologous BM depleted of both CD2+ and CD20+ cells. No new antibody directed against pig non-aGal antigens was detected in any baboon during the 1 month follow-up period. CONCLUSIONS: (i) EIA of anti-alphaGal antibody in unmodified baboons results in a transient depletion followed by a mild rebound of antibody; (ii) exposure to pig BM cells results in a substantial increase in anti-alphaGal antibody production; (iii) a nonmyeloablative conditioning regimen reduces the rate of antibody return and (iv) markedly reduces the response to pig BM cells; (v) the anti-alphaGal response is completely suppressed by a myeloablative regimen if CD2+ and CD20+ cells are eliminated from the autologous BM inoculum. Furthermore, (vi) challenge with pig BM cells appears to stimulate only an anti-alphaGal antibody response without the development of other (non-alphaGal) anti-pig antibodies. We conclude that regimens used for T-cell tolerance induction can be beneficial in reducing the anti-alphaGal antibody response to porcine BM.

Animals↗
PubMed2000

Contextual fear conditioning and baseline startle responses in the rat fear-potentiated startle test: a comparison of benzodiazepine/gamma-aminobutyric acid-A receptor agonists.

In the rat, fear-potentiated startle (FPS) test animals are first trained to associate brief light presentations with a mild electric footshock and then tested for startle responses to acoustic stimuli, delivered either in darkness (i.e. baseline startle) or after the conditioning stimulus. Following light presentation the magnitude of the startle response is markedly increased, and the test is commonly used to distinguish anxiolytic drug effects (i.e. a reduction in FPS) from non-specific effects such as sedation/muscle relaxation. However, recent studies suggest that the environment in which the animal is trained may also contribute towards the acquisition of a conditioned fear response (i.e. contextual fear conditioning) and that this may elevate startle responses recorded in the dark. In the present study, therefore, we have compared the benzodiazepine/gamma-aminobutyric acid-A receptor agonist chlordiazepoxide with the partial agonists FG 8205 and bretazenil, which are known to have a reduced propensity to produce sedation/myorelaxation, using two different FPS procedures: (i) conditioning and testing in stabilimeter chambers, and (ii) conditioning and testing in different environments. The results show that FPS can be demonstrated in both procedures and that treatment with chlordiazepoxide, FG 8205 or bretazenil dose-dependently attenuates the response. However, animals conditioned and tested in stabilimeter chambers also showed a significant increase in dark-startle amplitudes compared with non-shocked rats, suggesting that this response was elevated by contextual fear conditioning. Furthermore, despite clear differences in side-effect liabilities, FG 8205 and bretazenil significantly reduced dark-startle responses, suggesting that this measure is also sensitive to the anxiolytic effects of benzodiazepines. In contrast, when animals were conditioned and tested in different environments, dark-startle responses were not significantly different from those recorded in non-shocked rats and treatment with FG 8205 or bretazenil had no effect. Thus, conditioning and testing animals in different environments may provide a more effective means of distinguishing anxiolytic from non-specific drug effects in the rat FPS test.

Animals↗
PubMedDate not supplied

Acquisition of a new-latency conditioned nictitating membrane response--major, but not complete, dependence on the ipsilateral cerebellum.

Classical conditioning of the nictitating membrane response (NMR) of rabbits is simple associative learning of a motor response. In several two-stage experiments, reversible inactivations of the deep cerebellar nuclei in stage 1 appeared to prevent acquisition of NMR conditioning in naive rabbits--no conditioned responses (CRs) were evident after inactivations were lifted in stage 2. Results of a three-stage experiment were different. When subjects were first trained with a light conditional stimulus (CS) in stage 1, reversible cerebellar inactivations during conditioning to a different, tone CS during stage 2 did not appear to prevent new learning because CRs to the tone CS were evident when the inactivation was lifted. Results from the two-stage experiments support the suggestion that the cerebellum is essential for the acquisition of NMR conditioning, but results from the three-stage experiment do not. Here, we use a three-stage design with different interstimulus intervals (ISIs) in stages 1 and 2. Because CRs develop with latencies-to-peak dependent on the ISI, learning during stage 1 can be dissociated from that accruing in stage 2. Complete inactivation of the ipsilateral cerebellar nuclei with muscimol substantially but not completely prevented learning with the second ISI during stage 2 because small CR peaks around the stage 2 ISI could be detected in some subjects after the inactivation had been lifted in stage 3. We suggest that the weak levels of conditioning possible during unilateral inactivation depend on the contralateral cerebellum or on extracerebellar circuitry and that these may be capable of supporting transfer of conditioning in a previous three-stage experiment. But, we confirm that normal NMR conditioning is critically dependent on the ipsilateral cerebellum.

Animals↗
PubMedDate not supplied

Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery.

Conditioned fear responses to a tone paired with footshock rapidly extinguish when the tone is presented in the absence of the shock. Rather than erase conditioning, extinction is thought to involve the formation of new memory. In support of this, extinguished freezing spontaneously recovers with the passage of time. It is not known, however, how long extinction memory lasts or whether extinction interferes with consolidation of conditioning if given on the same day. To address this, we gave rats 7 trials of auditory fear conditioning followed 1 h later by 20 extinction trials, and tested for spontaneous recovery after a delay of 0, 1, 2, 4, 6, 10, or 14 d. Conditioned freezing to the tone gradually recovered with time to reach 100% by day 10. No-extinction controls indicated that the increase in freezing with time was not owing to incubation of conditioning memory. Complete spontaneous recovery indicates that extinction training given 1 h after conditioning does not interfere with the consolidation of conditioning memory. Despite complete recovery of freezing, rats showed savings in their rate of re-extinction, indicating persistence of extinction memory. These data support the idea that conditioning and extinction of fear are learned by independent systems, each able to retain a long-term memory.

Acoustic Stimulation↗
PubMed2000

Computer-assisted behavioral assessment of Pavlovian fear conditioning in mice.

In Pavlovian fear conditioning, a conditional stimulus (CS, usually a tone) is paired with an aversive unconditional stimulus (US, usually a foot shock) in a novel context. After even a single pairing, the animal comes to exhibit a long-lasting fear to the CS and the conditioning context, which can be measured as freezing, an adaptive defense reaction in mice. Both context and tone conditioning depend on the integrity of the amygdala, and context conditioning further depends on the hippocampus. The reliability and efficiency of the fear conditioning assay makes it an excellent candidate for the screening of learning and memory deficits in mutant mice. One obstacle is that freezing in mice has been accurately quantified only by human observers, using a tedious method that can be subject to bias. In the present study we generated a simple, high-speed, and highly accurate algorithm that scores freezing of four mice simultaneously using NIH Image on an ordinary Macintosh computer. The algorithm yielded a high correlation and excellent linear fit between computer and human scores across a broad range of conditions. This included the ability to score low pretraining baseline scores and accurately mimic the effects of two independent variables (shock intensity and test modality) on fear. Because we used a computer and digital video, we were able to acquire a secondary index of fear, activity suppression, as well as baseline activity scores. Moreover, we measured the unconditional response to shock. These additional measures can enhance the sensitivity of the assay to detect interesting memory phenotypes and control for possible confounds. Thus, this computer-assisted system for measuring behavior during fear conditioning allows for the standardized and carefully controlled assessment of multiple aspects of the fear conditioning experience.

Algorithms↗
PubMed1996

Dissociations in hippocampal 5-hydroxytryptamine release in the rat following Pavlovian aversive conditioning to discrete and contextual stimuli.

The experiments examined the release of 5-hydroxytryptamine using in vivo microdialysis methods in the hippocampus of freely moving rats following Pavlovian aversive conditioning to discrete and contextual stimuli. Differential conditioning was achieved by manipulating the interval between the offset of a discrete auditory 'clicker' stimulus and the onset of a mild foot-shock reinforcer (0.5 mA, 0.5 s). Foot-shock occurred either simultaneously with the last second of the discrete auditory stimulus (in short-trace subjects) or 60 s later (long-trace subjects). In this way, subjects were preferentially conditioned to the discrete stimulus and background 'contextual' stimuli respectively. During conditioning subjects also received two identical unpaired visual stimuli. At test, dialysates were collected and behavioural measures taken as all animals experienced (i) the aversive and two other 'neutral' environments, and (ii) the discrete unconditioned and conditioned stimuli presented in both aversive and neutral environments. Exposure to the aversive environment, but not to either of the two neutral environments, was associated with significantly increased hippocampal 5-hydroxytryptamine release in long-trace subjects. There was also a small but non-significant increase in 5-hydroxytryptamine release in short-trace animals. In contrast, hippocampal 5-hydroxytryptamine release was unaffected by presentation of either of the discrete stimuli under all conditions. The last result was obtained despite robust behavioural responses (freezing) to the discrete conditioned stimulus. These data do not agree with the hypothesis that aversive cues generally activate 5-hydroxytryptamine function in the hippocampus. Rather, they suggest a degree of specificity whereby 5-hydroxytryptamine release in the hippocampus was determined primarily by other qualitative properties of the conditioned aversive stimulus, namely whether the aversive cue was discrete or contextual, as well as by the magnitude of conditioning.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2004

NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala.

We examined the contribution of N-methyl-D-aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single-unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist +/--3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single-unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single-unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long-term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning-related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.

Action Potentials↗
PubMed1994

Nonconscious associative learning: Pavlovian conditioning of skin conductance responses to masked fear-relevant facial stimuli.

We examined the possibility of nonconscious associative learning in a context of skin conductance conditioning, using emotional facial expressions as stimuli. In the first experiment, subjects were conditioned to a backwardly masked angry face that was followed by electric shock, with a masked happy face as the nonreinforced stimulus. In spite of the effectively masked conditioned stimuli, differential conditioned skin conductance responses were observed in a subsequent nonmasked extinction phase. This effect could not be attributed to differential sensitization or pseudo-conditioning. In the second experiment, the differential responding during extinction was replicated with angry but not with happy faces as conditioned stimuli. It was concluded that with fear-relevant facial expressions as the conditioned stimulus, associative learning was possible even in conditions where the subjects remained unaware of the conditioned stimulus and its relationship to the unconditioned stimulus.

Adult↗
PubMed1996

Sweat fluid and ion losses in horses during training and competition in cool vs. hot ambient conditions: implications for ion supplementation.

The objectives of this study were to: 1) determine incremental and total sweat fluid and ion losses during and following (a) exercise training and (b) a treadmill Speed and Endurance exercise test (SEET) which simulated running speeds and distances required for each phase of an Olympic level (CCI****) 3-day-event in cool and hot ambient conditions and 2) determine the requirement for ion supplementation based on the calculated ion losses associated with these activities. Six exercise-trained Thoroughbred horses completed 2 weeks of exercise training in each of 2 ambient conditions: cool, dry (CD, room temperature [T] = 20-22 degrees C, relative humidity [RH] = 45-55%), or hot and humid (HH, T = 33-35 degrees C, RH = 80-85%). Following the 2 week period of training in either CD or HH conditions, horses completed a SEET under similar conditions (either CD, or hot and dry (HD, T = 33-35 degrees C, RH = 45-55%). Sweating rate and sweat ion composition for each 5 min interval was determined from sweat samples collected from a sealed pouch attached to the lateral thorax. Total sweat fluid losses during training in the heat were 2- or 3-fold greater when compared to CD. Similarly, sweat fluid losses associated with the SEET in HD were almost double (19.2 litres) the losses in CD (11.7 litres). Total calculated ion losses associated with 2 h of training in HH (3724 mmol; 115.2 g) were significantly greater when compared to CD (1413 mmol; 43.5 g). Following the SEET and a 30 min recovery period, total ion losses in CD were 3636 mmol (112.2 g) compared with 6519 mmol (200.6 g) in HD. The differences in ion losses represent the increased sweating rates stimulated by higher core temperatures during moderate to high intensity exercise in warmer ambient conditions and increases in sweat ion concentrations associated with higher sweating rates. Extracellular fluid (ECF) ion losses during daily exercise training and the SEET were also calculated from changes in plasma ion concentrations and ECF volume. Calculated ECF ion losses were significantly higher in hot ambient conditions but were approximately 50% less than calculated sweat ion losses. The calculated sweat ion losses incurred during daily exercise training in hot and humid ambient conditions are > 3-fold higher than losses measured following exercise training in cooler conditions. Whereas fluid regulating hormones may have reduced urinary and faecal losses of ions during 2 weeks of training in HH, the quantity of sodium, potassium and chloride calculated to have been lost in sweat during the SEET in HD exceeded the daily dietary intake of these ions and suggests the need for appropriate ion supplementation during training and competition in hot ambient conditions.

Animals↗
PubMed2003

Development of reorganization of the auditory cortex caused by fear conditioning: effect of atropine.

Reorganization of the frequency map in the central auditory system is based on shifts in the best frequencies (BFs; hereafter, BF shifts), together with the frequency-response curves, of auditory neurons. In the big brown bat, conditioning with acoustic stimulation followed by electric leg-stimulation causes BF shifts of collicular and cortical neurons. The collicular BF shift develops quickly and is short term, whereas the cortical BF shift develops slowly and is long term. The acetycholine level in the auditory cortex must be high during conditioning to develop these BF shifts. We studied the effect of atropine (an antagonist of muscarinic acetylcholine receptors) applied to the auditory cortex on the development of the long-term cortical BF shift in the awake bat caused by a 30-min conditioning session. We found 1) the cortical BF shift starts to develop approximately 15 min after the onset of the conditioning, gradually increases over 60 min, and reaches a plateau, 2) the cortical BF shift changes from short to long term approximately 45 min after the onset of the conditioning, 3) the cortical BF shift can plateau at different frequencies between the BF of a given neuron in the control condition and the frequency of the conditioning tone, 4) the maximum BF shift is determined approximately 70 min after the onset of the conditioning, and 5) acetylcholine plays an important role in the development of the cortical BF shift. Its role ends approximately 180 min after the onset of the conditioning.

Acoustic Stimulation↗
PubMed1989

Memory traces in primate spinal cord produced by operant conditioning of H-reflex.

1. Study of memory traces in higher animals requires experimental models possessing well-localized and technically accessible memory traces--plasticity responsible for behavioral change, not dependent on control from elsewhere, and open to detailed investigation. Our purpose has been to develop such a model based on the wholly spinal, largely monosynaptic path of the spinal stretch reflex. Previous studies described operant conditioning of this reflex and of its electrical analog, the H-reflex. In this study, we sought to determine whether conditioning causes changes in the spinal cord that affect the reflex and are not dependent on continued supraspinal influence, and thus qualify as memory traces. 2. Sixteen monkeys underwent chronic conditioning of the triceps surae H-reflex. Eight were rewarded for increasing H-reflex amplitude (HR increases mode), and eight were rewarded for decreasing it (HR decreases mode). In each animal, the other leg was an internal control. Over several months of conditioning, H-reflex amplitude in the conditioned leg rose in HR increases animals and fell in HR decreases animals. H-reflex amplitude in the control leg changed little. 3. After HR increases or HR decreases conditioning, each animal was deeply anesthetized and surgically prepared. The reflex response to supramaximal dorsal root stimulation was measured from the triceps surae nerve as percent of response to supramaximal ventral root stimulation, which was the maximum possible response. Data from both legs were collected before and for up to 3 days after thoracic (T9-10) cord transection. The animal remained deeply anesthetized throughout and was killed by overdose. 4. The reflex asymmetries produced by conditioning were still present several days after transection removed supraspinal influence: reflexes of HR increases animals were significantly larger in HR increases legs than in control legs and reflexes of HR decreases animals were significantly smaller in HR decreases legs than in control legs. 5. Reflex amplitude was much greater in the control legs of anesthetized HR decreases animals than in the control legs of anesthetized HR increases animals. 6. Chronic conditioning had at least two effects on the spinal cord. The first effect, task-appropriate reflex asymmetry, was evident both in the awake behaving animal and in the anesthetized transected animal. The second effect, larger control leg reflexes in HR decreases than in HR increases animals, was evident only in the anesthetized animal. By removing supraspinal control, anesthesia and transection revealed a previously hidden effect of conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

In vitro appetitive classical conditioning of the feeding response in the pond snail Lymnaea stagnalis.

In vitro appetitive classical conditioning of the feeding response in the pond snail Lymnaea stagnalis. J. Neurophysiol. 78: 2351-2362, 1997. An in vitro preparation was developed that allowed electrophysiological analysis of appetitive conditioning of feeding in the model molluscan system, Lymnaea. The network generating the feeding motor program (fictive feeding) is well characterized at the cellular level and consists of identified central pattern generator (CPG) interneurons, motor neurons, and modulatory interneurons. Activation of a modulatory interneuron, the slow oscillator (SO), evokes the three-phase fictive feeding rhythm in the same semi-intact preparations where tactile stimuli can be applied to the lips. By pairing touch as a conditioned stimulus (CS) with stimulation of the SO as an unconditioned stimulus (US), we established an effective in vitro paradigm for appetitive conditioning. Before training, touch to the lips evoked only brief and weak activity in the feeding interneurons and motor neurons. After 6-10 conditioning trials, there was a significant enhancement in the fictive feeding response to CS alone. This was not seen in controls (CS only, US only, random CS and US) and in preparations where there was no initial brief response to touch before conditioning. Direct recordings from the protraction phase N1M interneurons during in vitro conditioning indicated that the enhancement of the fictive feeding is due to an increased activation of these CPG cells by mechanosensory inputs from the lips. We also found that the conditioned response was not due to a facilitated activation of modulatory neurons in the feeding network, such as the SO or the cerebral giant cells (CGCs), because the activity of these cells remained unchanged after conditioning.

Animals↗
PubMed1998

Neurophysiological correlates of unconditioned and conditioned feeding behavior in the pond snail Lymnaea stagnalis.

We used a behavioral appetitive learning paradigm followed by electrophysiological analysis to investigate the neuronal expression of appetitive conditioning in Lymnaea. We first established the levels of unconditioned and conditioned feeding responses in intact animals. We then demonstrated that neuronal correlates of both unconditioned responses to touch and food and a conditioned response to touch could be found in semi-intact preparations of the same animals that had been subjected to behavioral tests and conditioning trials. In the conditioning experiments, the experimental animals received 15 trials in which touch to the lips, the conditioned stimulus (CS), was paired with sucrose, the unconditioned food stimulus (US). Control animals received 15 presentations of either CS or US, or both, applied in a random manner. After training, a strong conditioned response to touch was established in the experimental but not in the control groups. For subsequent electrophysiological analysis of posttraining neuronal responses to the touch CS, semi-intact preparations were set up from the same animals that had been behaviorally conditioned or subjected to control procedures. Intracellular recordings, made from previously identified motoneurons of the feeding system, allowed the fictive feeding response to the CS to be monitored. In experimental preparations, touch applied to the lips evoked significantly more fictive feeding cycles than in controls, and this demonstrated the existence of a neurophysiological correlate of the appetitively conditioned response observed in the whole animals.

Animals↗
PubMed1999

Long-term sound conditioning enhances cochlear sensitivity.

Sound conditioning, by chronic exposure to moderate-level sound, can protect the inner ear (reduce threshold shifts and hair cell damage) from subsequent high-level sound exposure. To investigate the mechanisms underlying this protective effect, the present study focuses on the physiological changes brought on by the conditioning exposure itself. In our guinea-pig model, 6-h daily conditioning exposure to an octave-band noise at 85 dB SPL reduces the permanent threshold shifts (PTSs) from a subsequent 4-h traumatic exposure to the same noise band at 109 dB SPL, as assessed by both compound action potentials (CAPs) and distortion product otoacoustic emissions (DPOAEs). The frequency region of maximum threshold protection is approximately one-half octave above the upper frequency cutoff of the exposure band. Protection is also evident in the magnitude of suprathreshold CAPs and DPOAEs, where effects are more robust and extend to higher frequencies than those evident at or near threshold. The conditioning exposure also enhanced cochlear sensitivity, when evaluated at the same postconditioning time at which the traumatic exposure would be delivered in a protection study. Response enhancements were seen in both threshold and suprathreshold CAPs and DPOAEs. The frequency dependence of the enhancement effects differed, however, by these two metrics. For CAPs, effects were maximum in the same frequency region as those most protected by the conditioning. For DPOAEs, enhancements were shifted to lower frequencies. The conditioning exposure also enhanced both ipsilaterally and contralaterally evoked olivocochlear (OC) reflex strength, as assessed using DPOAEs. The frequency and level dependence of the reflex enhancements were consistent with changes seen in sound-evoked discharge rates in OC fibers after conditioning. However, comparison with the frequency range and magnitude of conditioning-related protection suggests that the protection cannot be completely explained by amplification of the OC reflex and the known protective effects of OC feedback. Rather, the present results suggest that sound conditioning leads to changes in the physiology of the outer hair cells themselves, the peripheral targets of the OC reflex.

Acoustic Stimulation↗
PubMed2001

Selective expression of electrical correlates of differential appetitive classical conditioning in a feeding network.

Electrical correlates of differential appetitive classical conditioning were recorded in the neural network that underlies feeding in the snail Lymnaea stagnalis. In spaced training (15 trials over 3 days), the lips and the tentacle were used as CS+ (reinforced conditioned stimulus) or CS- (nonreinforced conditioned stimulus) sites for behavioral tactile conditioning. In one group of experimental animals, touch to the lips (the CS+ site) was followed by sucrose (the unconditioned stimulus, US), but touch to the tentacle (the CS- site) was not reinforced. In a second experimental group the CS+/CS- sites were reversed. Semi-intact lip-tentacle-CNS preparations were made from both experimental groups and a naive control group. Intracellular recordings were made from the B3 motor neuron of the feeding network, which allowed the monitoring of activity in the feeding central pattern generator (CPG) interneurons as well as early synaptic inputs evoked by the touch stimulus. Following successful behavioral conditioning, the touch stimulus evoked CPG-driven fictive feeding activity at the CS+ but not the CS- sites in both experimental groups. Naive snails/preparations showed no touch responses. A weak asymmetrical stimulus generalization of conditioned feeding was not retained at the electrophysiological level. An early excitatory postsynaptic potential (EPSP) response to touch was only enhanced following conditioning in the Lip CS+/tentacle CS- group but not in the Tentacle CS+/lip CS- group. The results show that the main features of differential appetitive classical conditioning can be recorded at the electrophysiological level, but some characteristics of the conditioned response are selectively expressed in the reduced preparation.

Animals↗