Amplitude Of Conditioned Response Research Articles

Conscious expectancy rather than associative strength elicits brain activity during single-cue fear conditioning.

The neurocognitive processes underlying Pavlovian conditioning in humans are still largely debated. The conventional view is that conditioned responses (CRs) emerge automatically as a function of the contingencies between a conditioned stimulus (CS) and an unconditioned stimulus (US). As such, the associative strength model asserts that the frequency or amplitude of CRs reflects the strength of the CS-US associations. Alternatively, the expectation model asserts that the presentation of the CS triggers conscious expectancy of the US, which is responsible for the production of CRs. The present study tested the hypothesis that there are dissociable brain networks related to the expectancy and associative strength theories using a single-cue fear conditioning paradigm with a pseudo-random intermittent reinforcement schedule during functional magnetic resonance imaging. Participants' (n = 21) trial-by-trial expectations of receiving shock displayed a significant linear effect consistent with the expectation model. We also found a positive linear relationship between the expectancy model and activity in frontoparietal brain areas including the dorsolateral prefrontal cortex (PFC) and dorsomedial PFC. While an exploratory analysis found a linear relationship consistent with the associated strength model in the insula and early visual cortex, our primary results are consistent with the view that conscious expectancy contributes to CRs.

Intracerebellar infusion of an mGluR1/5 agonist enhances eyeblink conditioning.

Cerebellar metabotropic glutamate receptor 1 (mGluR1) expressed by Purkinje cells may play an important role in learning-related cerebellar plasticity. Eyeblink conditioning (EBC) is a well-studied form of Pavlovian learning that engages discrete areas of cerebellar cortex and deep cerebellar nuclei. EBC is impaired in mGluR1 knockout mice. Here, we show that infusion of the mGluR1/5 agonist DHPG into the lobulus simplex region of cerebellar cortex facilitates EBC in rats. Infusion was made prior to Sessions 1 and 2 of EBC but the facilitatory effects persisted throughout subsequent, noninfusion sessions. The facilitatory effects were confined to frequency of eyeblink conditioned responses (CRs); there were no effects on amplitude or latency of CRs. There were also no effects on reflexive responding to the tone conditioned stimulus or eyelid stimulation unconditioned stimulus. The current results provide further evidence that cerebellar mGluR1 plays a role in cerebellar-dependent associative learning and complement previous studies using mGluR1 knockout mice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Systematic variation of acquisition rate in delay eyelid conditioning.

Averaging artifacts inherent in group acquisition curves can mask behavioral phenomena that are potentially revealing in terms of underlying neural mechanisms. To address this, we implemented a behavioral analysis of 106 rabbits trained over 4 sessions using delay eyelid conditioning. Group results showed the typical monotonic increase in conditioned responses (CRs). For most subjects CRs first appeared (as indexed by the criterion of 8 CRs in 9 trials) during the first 18 trials of the second training session. Subdividing subjects according to the training block at which they met criterion revealed systematic differences in the subsequent rate that CR amplitudes increased, but not in asymptotic CR amplitudes. Subjects meeting criterion early in sessions showed more rapid increases in CR amplitude than those meeting criterion later in sessions. This effect was solely dependent on how early within a session criterion was met, as subjects meeting criterion at the beginning of the third and fourth sessions showed more rapid increases in CR amplitude than those meeting criterion after the first 18 trials of the second session. The exceptions were the 7% of the subjects that met criterion late in the first session. Their CR amplitudes increased at a rate similar to subjects meeting criterion early in sessions. These results suggest an interplay between consolidation processes and a previously reported short-term plasticity process that makes CR acquisition a nonmonotonic and complex function of the point during training sessions at which CRs first appear. (PsycINFO Database Record

The Motor Cortex Is Involved in the Generation of Classically Conditioned Eyelid Responses in Behaving Rabbits.

Classical blink conditioning is a well known model for studying neural generation of acquired motor responses. The acquisition of this type of associative learning has been related to many cortical, subcortical, and cerebellar structures. However, until now, no one has studied the motor cortex (MC) and its possible role in classical eyeblink conditioning. We recorded in rabbits the activity of MC neurons during blink conditioning using a delay paradigm. Neurons were identified by their antidromic activation from facial nucleus (FN) or red nucleus (RN). For conditioning, we used a tone as a conditioned stimulus (CS) followed by an air puff as an unconditioned stimulus (US) that coterminated with it. Conditioned responses (CRs) were determined from the electromyographic activity of the orbicularis oculi muscle and/or from eyelid position recorded with the search coil technique. Type A neurons increased their discharge rates across conditioning sessions and reached peak firing during the CS-US interval, while type B cells presented a second peak during US presentation. Both of them project to the FN. Type C cells increased their firing across the CS-US interval, reaching peak values at the time of US presentation, and were activated from the RN. These three types of neurons fired well in advance of the beginning of CRs and changed with them. Reversible inactivation of the MC during conditioning evoked a decrease in learning curves and in the amplitude of CRs, while train stimulation of the MC simulated the profile and kinematics of conditioned blinks. In conclusion, MC neurons are involved in the acquisition and expression of CRs. Classical blink conditioning is a popular experimental model for studying neural mechanisms underlying the acquisition of motor skills. The acquisition of this type of associative learning has been related to many cortical, subcortical, and cerebellar structures. However, until now, no one has studied the motor cortex (MC) and its possible role in classical eyeblink conditioning. Here, we report that the firing activities of MC neurons, recorded in behaving rabbits, are related to and preceded the initiation of conditioned blinks. MC neurons were identified as projecting to the red or facial nuclei and encoded the kinematics of conditioned eyelid responses. The timed stimulation of recording sites simulated the profile of conditioned blinks. MC neurons play a role in the acquisition and expression of these acquired motor responses.

Eyelid conditioning to a target amplitude: adding how much to whether and when.

Conceptual and practical advantages of pavlovian eyelid conditioning facilitate analysis of cerebellar computation and learning. Even so, eyelid conditioning procedures are unrealistic in an important way. The error signal to the olivocerebellar system does not decrease as learning adapts response amplitude or gain. This inherently limits the utility of eyelid conditioning for studies investigating how cerebellar learning mechanisms acquire and store an adaptive response amplitude. We report the development and characterization of a training procedure in which conditioned response amplitude is brought under experimental control with contingencies that more closely parallel natural conditions. In this procedure, the delivery of the unconditioned stimulus (US) is made contingent on conditioned response amplitude: the US is delivered for responses that fail to reach a specified target amplitude and is omitted for responses that meet or exceed the target. We find that rabbits trained with either a tone or with mossy fiber stimulation as the conditioned stimulus learn responses that approach target amplitudes ranging from 2 to 5 mm. Inactivating the interpositus nucleus with muscimol infusions abolished these conditioned responses, indicating that cerebellar involvement in eyelid conditioning is not tied explicitly to the use of pavlovian procedures. Together with previous studies, these data suggest that response amplitude is learned and encoded in the cerebellum during eyelid conditioning. As such, these results provide a foundation for systematic and controlled investigations of the cerebellar mechanisms that learn and encode the proper amplitude of adaptive movements.

Evidence From Retractor Bulbi EMG for Linearized Motor Control of Conditioned Nictitating Membrane Responses

Classical conditioning of nictitating membrane (NM) responses in rabbits is a robust model learning system, and experimental evidence indicates that conditioned responses (CRs) are controlled by the cerebellum. It is unknown whether cerebellar control signals deal directly with the complex nonlinearities of the plant (blink-related muscles and peripheral tissues) or whether the plant is linearized to ensure a simple relation between cerebellar neuronal firing and CR profile. To study this question, the retractor bulbi muscle EMG was recorded with implanted electrodes during NM conditioning. Pooled activity in accessory abducens motoneurons was estimated from spike trains extracted from the EMG traces, and its temporal profile was found to have an approximately Gaussian shape with peak amplitude linearly related to CR amplitude. The relation between motoneuron activity and CR profiles was accurately fitted by a first-order linear filter, with each spike input producing an exponentially decaying impulse response with time constant of order 0.1 s. Application of this first-order plant model to CR data from other laboratories suggested that, in these cases also, motoneuron activity had a Gaussian profile, with time-of-peak close to unconditioned stimulus (US) onset and SD proportional to the interval between conditioned stimulus and US onsets. These results suggest that for conditioned NM responses the cerebellum is presented with a simplified "virtual" plant that is a linearized version of the underlying nonlinear biological system. Analysis of a detailed plant model suggests that one method for linearising the plant would be appropriate recruitment of motor units.

Response linearity determined by recruitment strategy in detailed model of nictitating membrane control

Many models of eyeblink conditioning assume that there is a simple linear relationship between the firing patterns of neurons in the interpositus nucleus and the time course of the conditioned response (CR). However, the complexities of muscle behaviour and plant dynamics call this assumption into question. We investigated the issue by implementing the most detailed model available of the rabbit nictitating membrane response (Bartha and Thompson in Biol Cybern 68:135-143, 1992a and in Biol Cybern 68:145-154, 1992b), in which each motor unit of the retractor bulbi muscle is represented by a Hill-type model, driven by a non-linear activation mechanism designed to reproduce the isometric force measurements of Lennerstrand (J Physiol 236:43-55, 1974). Globe retraction and NM extension are modelled as linked second order systems. We derived versions of the model that used a consistent set of SI units, were based on a physically realisable version of calcium kinetics, and used simulated muscle cross-bridges to produce force. All versions showed similar non-linear responses to two basic control strategies. (1) Rate-coding with no recruitment gave a sigmoidal relation between control signal and amplitude of CR, reflecting the measured relation between isometric muscle force and stimulation frequency. (2) Recruitment of similar strength motor units with no rate coding gave a sublinear relation between control signal and amplitude of CR, reflecting the increase in muscle stiffness produced by recruitment. However, the system response could be linearised by either a suitable combination of rate-coding and recruitment, or by simple recruitment of motor units in order of (exponentially) increasing strength. These plausible control strategies, either alone or in combination, would in effect present the cerebellum with the simplified virtual plant that is assumed in many models of eyeblink conditioning. Future work is therefore needed to determine the extent to which motor neuron firing is in fact linearly related to the nictitating membrane response.

Combat veterans show normal discrimination during differential trace eyeblink conditioning, but increased responsivity to the conditioned and unconditioned stimulus

The question addressed in the present study was whether post-traumatic stress disorder (PTSD) results in associative learning impairments. To answer this question, differential trace eyeblink (EB) conditioning was studied in combat veterans with PTSD, combat veterans without PTSD, and non-combat veterans without PTSD. Veterans with PTSD showed normal EB discrimination, suggesting that associative learning is not impaired by PTSD. Veterans with PTSD also showed normal extinction. However, subjects with PTSD showed more EB conditioned responses (CRs), as well as increased CR amplitude. Increased response amplitude to the airpuff unconditioned stimulus presented alone (viz. the unconditioned response), as well as to the airpuff on CS+ trials during conditioning also occurred in the subjects with PTSD. These findings suggest increased reactivity in combat veterans with PTSD, compared to those without PTSD, but such heightened reactivity does not affect somatomotor associative learning.

The ontogeny of interstimulus interval (ISI) discrimination of the conditioned eyeblink response in rats.

Discrimination of the eyeblink conditioned response (CR) between conditioned stimuli (CSs) of different durations and modalities was examined across development in rats. Interstimulus interval (ISI) discrimination was evident at Postnatal Days 23-34 in Experiment 1, and earlier CR peak latencies and enhanced CR amplitudes were seen to the long CS in the ISI discrimination group relative to a control group receiving the short CS without reinforcement. Experiment 2 showed that early CR peak latencies and enhanced CR amplitudes to the long CS in the ISI discrimination group were due to associative pairing of the short CS and unconditioned stimulus. Experiment 3 demonstrated ISI discrimination in adults that was improved relative to younger subjects, but with no enhancement of CR amplitude to the long CS in the ISI discrimination group. Cerebellar cortical maturation may influence the ontogeny of CR timing.

Abnormalities of cortical excitability and cortical inhibition in cervical dystonia Evidence from somatosensory evoked potentials and paired transcranial magnetic stimulation recordings.

Cortical excitability and cortico-cortical inhibition were examined in twenty-one patients suffering from idiopathic rotational cervical dystonia. Polymyography of cervical muscles, somatosensory evoked potential recordings, and paired transcranial magnetic stimulation were used to assess the dystonic disorder. The results were compared with those obtained in a group of sixteen healthy age-matched volunteers. Statistically significant differences between the patient group and the control group were found when the amplitude values of the mean P22/N30 component measured at F [3, 4] and C[3, 4]' electrode positions were compared. The mean amplitude of P22/N30 in both of these electrode positions contralaterally to the direction of head deviation was significantly higher in the patient group (p <or= 0.05). The mean side-to-side P22/N30 amplitude ratio was calculated in both groups in the F[3, 4] and C[3, 4]' electrode positions: there was a significant difference between the two groups. The mean ratio (calculated contralaterally/ipsilaterally in the patient group and left/right side in the control group) was significantly higher in the patient group (p <or= 0.05). There were statistically significant differences between the two groups when the mean values of MEP amplitudes following paired stimuli at short and medium interstimulus intervals (ISI)) were compared. The percentage of amplitude reduction registered at short ISI was significantly lower in the patient group when both 3 ms ISI and 5 ms ISI were considered, and when the hemisphere contralateral to the direction of head deviation was stimulated. There was also a difference (with the short ISI) when the hemisphere ipsilateral to the direction of head deviation was stimulated, but this difference was not significant (p < 0.5). Almost all of the amplitude changes following the paired stimulus at the longer ISI, i. e. 10, 15, and 20 ms were significantly different when the patient group was compared with control group: when the ipsilateral hemisphere was stimulated, the amplitude of conditioned responses was significantly higher following all three paired stimuli (with 10, 15, and 20 ms ISI) at the p <or= 0.05 significance level; when the contralateral hemisphere was stimulated, they were significantly higher following the 10 and 20 ms ISI paired stimuli (significance level p <or= 0.05). The interhemispheric difference in the patient group was significant only for the paired stimuli using 3 and 5 ms (short) ISI and 15 and 20 ms (medium) ISI. There was a significantly decreased inhibition at 3 and 5 ms ISI when the hemisphere contralateral to the direction of head deviation was stimulated, as compared with the hemisphere ipsilateral (p <or= 0.05). Similarly, there was a significantly increased facilitation at 15 and 20 ms when the hemisphere contralateral to the direction of head deviation was stimulated, as compared with the hemisphere ipsilateral (p <or= 0.05). The results indicate that a disorder of both cortical excitability and intracortical inhibition exists in patients with cervical dystonia, and that this disorder is lateralized, i. e. it is located within the hemisphere contralateral to the direction of head deviation.

An Experimental Study of Posterior Interpositus Involvement in the Genesis and Control of Conditioned Eyelid Responses

The participation of the rostral-dorsal part of the posterior interpositus nucleus in the genesis of classically-conditioned eyelid responses in alert cats was studied. Cats were prepared for the recording of left eyelid movements with the search-coil-in-a-magnetic-field technique and of the electromyographic activity of the orbicularis oculi muscle. A stimulating electrode was implanted in the contralateral red nucleus and a guide cannula in the ipsilateral interpositus. The cannula allowed unitary recordings, electrical microstimulation, drug injection, and push-pull perfusion of the selected interpositus site. Perfusate was used for amino acid analysis with an HPLC-EC method. Animals were conditioned with a delay (CS: tone, US: air puff) paradigm. Antidromically identified interpositus neurons fired during eyelid conditioned responses (CRs) with a variable delay to CR start. Some neurons (type A) increased and other (type B) decreased their firing during CR performance. Electrical microstimulation of posterior interpositus was able to increase CR amplitude when applied during CS presentation. Muscimol decreased CR amplitude in well-trained animals. The analysis of push-pull perfusate showed a significant increase in glutamate, glycine, and taurine, but not GABA levels, during conditioning in comparison with habituation and extinction periods. Results indicate an involvement of the rostral-dorsal part of the posterior interpositus nucleus in the genesis of eyelid conditioned responses, playing an enhancing or controlling role in CR performance, rather than being its initiator.

Latent Acquisition of Timed Responses in Cerebellar Cortex

Evidence indicates that rabbit eyelid conditioning is mediated by plasticity in the interpositus cerebellar nucleus and in cerebellar cortex. Although the relative contributions of these sites are not fully characterized, evidence suggests that plasticity in the cerebellar cortex influences conditioned response amplitude and timing, whereas plasticity in the interpositus nucleus is necessary or permissive for conditioned response expression. Recent empirical and computational analyses suggest that, during training, plasticity is initially established in the cerebellar cortex, whereas conditioned response expression begins later as plasticity is induced in the interpositus nucleus. We used the dependence of response timing on the interstimulus interval (ISI) to test this latent learning hypothesis. Rabbits were initially trained using a tone conditioned stimulus (CS) with a relatively long ISI to a low-criterion threshold. The relative absence of plasticity in the interpositus nucleus was then examined via reversible disconnection of the cerebellar cortex. Later, to induce plasticity in the interpositus nucleus, subjects were trained to robust levels of conditioned response expression using a shorter ISI. Reversible disconnection of the cerebellar cortex at this time confirmed the presence of robust interpositus nucleus plasticity after the second phase. Subsequent probe trials with the long CS alone then revealed double-peaked responses whose peaks were appropriately timed to the two ISIs. The results are consistent with the hypothesis that temporally specific learning occurs first in the cerebellar cortex before the appearance of conditioned responses. This latent learning is expressed only after plasticity is induced in the interpositus nucleus.

Ontogenetic changes in the neural mechanisms of eyeblink conditioning.

The rodent eyeblink conditioning paradigm is an ideal model system for examining the relationship between neural maturation and the ontogeny of associative learning. Elucidation of the neural mechanisms underlying the ontogeny of learning is tractable using eyeblink conditioning because the necessary neural circuitry (cerebellum and interconnected brainstem nuclei) underlying the acquisition and retention of the conditioned response (CR) has been identified in adult organisms. Moreover, the cerebellum exhibits substantial postnatal anatomical and physiological maturation in rats. The eyeblink CR emerges developmentally between postnatal day (PND) 17 and 24 in rats. A series of experiments found that the ontogenetic emergence of eyeblink conditioning is related to the development of associative learning and not related to changes in performance. More recent studies have examined the relationship between the development of eyeblink conditioning and the physiological maturation of the cerebellum, a brain structure that is necessary for eyeblink conditioning in adult organisms. Disrupting cerebellar development with lesions or antimitotic treatments impairs the ontogeny of eyeblink conditioning. Studies of the development of physiological processes within the cerebellum have revealed striking ontogenetic changes in stimulus-elicited and learning-related neuronal activity. Neurons in the interpositus nucleus and Purkinje cells in the cortex exhibit developmental increases in neuronal discharges following the unconditioned stimulus (US) and in neuronal discharges that model the amplitude and time-course of the eyeblink CR. The developmental changes in CR-related neuronal activity in the cerebellum suggest that the ontogeny of eyeblink conditioning depends on the development of mechanisms that establish cerebellar plasticity. Learning and the induction of neural plasticity depend on the magnitude of the US input to the cerebellum. The role of developmental changes in the efficacy of the US pathway has been investigated by monitoring neuronal activity in the inferior olive and with stimulation techniques. The results of these experiments indicate that the development of the conditioned eyeblink response may depend on dynamic interactions between multiple developmental processes within the eyeblink neural circuitry.

Cerebellar posterior interpositus nucleus as an enhancer of classically conditioned eyelid responses in alert cats.

Cerebellar posterior interpositus neurons were recorded in cats during delayed and trace conditioning of eyeblinks. Type A neurons increased their firing in the time interval between conditioned and unconditioned stimulus presentations for both paradigms, while type B neurons decreased it. The discharge of different type A neurons recorded across successive conditioning sessions increased, with slopes of 0.061-0.078 spikes/s/trial. Both types of neurons modified their firing several trials in advance of the appearance of eyelid conditioned responses, but for each conditioned stimulus presentation their response started after conditioned response onset. Interpositus microstimulation evoked eyelid responses similar in amplitude and profiles to conditioned responses, and microinjection of muscimol decreased conditioned response amplitude. It is proposed that the interpositus nucleus is an enhancer, but not the initiator, of eyelid conditioned responses.

The Conditioned Eyeblink Response: A Role for the GABA-B Receptor?

In well-trained animals, infusion of the GABA-B agonist baclofen into the cerebellar interpositus nucleus and overlying cortex abolished the conditioned response (CR) with no effect on the unconditioned response (UR) with doses at or above 5.0 mM. Infusion of the GABA-B antagonist CGP 5584-5A alone had no effect on the CR or UR. However, administration of 5 mM baclofen soon after infusion of CGP 5584-5A (15 min) resulted in no reduction of percent CR and only partial reduction of CR amplitude. Naive animals given interpositus infusions of baclofen during training showed no learning, yet learned normally in postinfusion training. The distribution of (radiolabelled) baclofen was localized and remained within the cerebellum. The results presented here are consistent with a growing body of literature supporting the hypothesis that the memory trace for eyeblink conditioning is formed and stored in the cerebellum and may involve GABAergic mechanisms.

Projections from the thoracic cord to the cerebellar nuclei in the rat

Kinematic and dynamic analyses were employed to study the effects of cerebellar lesions on conditioned and unconditioned nictitating membrane responses in the rabbit. It was found that conditioned responses acquired to an auditory stimulus accelerated in two bursts as indicated by two distinct peaks of acceleration. The second peak of acceleration was very weak during the early portions of conditioning but became a prominent feature of the conditioned response over 16 sessions of conditioning. The second peak of acceleration in the conditioned response was more sensitive to cerebellar damage than was the first peak. When lesions of the cerebellum permanently reduced the amplitude of conditioned responses, but did not affect their frequency, the second peak of acceleration was nearly abolished while the first peak was unaffected. When cerebellar lesions profoundly impaired both the amplitude and frequency of conditioned responses, large and permanent impairments occurred in both peaks of acceleration. Lesions of the anterior interpositus nucleus most severely impaired both peaks of acceleration in the conditioned response and significantly reduced the acceleration of unconditioned responses across a wide range of intensities of corneal air puff. The deficit in the acceleration of unconditioned responses became manifest only after membrane extension exceeded 0.12 mm. The impairment in the amplitude of the unconditioned response after cerebellar lesions more closely approximated the impairment in the amplitude of the conditioned response when the force-generating properties of the conditioned and unconditioned stimuli were equated. It was hypothesized, therefore, that one reason why conditioned responses are so easily disrupted by cerebellar lesions is because they are of low force and not simply because they are learned.It was proposed that the two peaks of acceleration that characterize the conditioned response represent the function of two distinct anatomical systems. The first, a short-latency system, initiates the response and is most likely mediated by circuits that traverse the pontomedullary reticular formation. The second, a longer-latency system, amplifies response amplitude and its neural basis remains to be elucidated. The two components of the conditioned response may reflect two sequential bursts of activity in the accessory abducens nucleus, the principal site of the motoneurons for the retractor bulbi muscle, or may reflect the synergistic activity of the accessory abducens nucleus and the motor nuclei of the other extraocular muscles. It was concluded that the vulnerability of the second component of the conditioned response to cerebellar damage reflects an important role for the cerebellum in modulating the degree to which long-latency neural systems contribute to the ongoing performance of learned and unlearned behaviors.

1503 Projections from the thoracic cord to the cerebellar nuclei in the rat

Kinematic and dynamic analyses were employed to study the effects of cerebellar lesions on conditioned and unconditioned nictitating membrane responses in the rabbit. It was found that conditioned responses acquired to an auditory stimulus accelerated in two bursts as indicated by two distinct peaks of acceleration. The second peak of acceleration was very weak during the early portions of conditioning but became a prominent feature of the conditioned response over 16 sessions of conditioning. The second peak of acceleration in the conditioned response was more sensitive to cerebellar damage than was the first peak. When lesions of the cerebellum permanently reduced the amplitude of conditioned responses, but did not affect their frequency, the second peak of acceleration was nearly abolished while the first peak was unaffected. When cerebellar lesions profoundly impaired both the amplitude and frequency of conditioned responses, large and permanent impairments occurred in both peaks of acceleration. Lesions of the anterior interpositus nucleus most severely impaired both peaks of acceleration in the conditioned response and significantly reduced the acceleration of unconditioned responses across a wide range of intensities of corneal air puff. The deficit in the acceleration of unconditioned responses became manifest only after membrane extension exceeded 0.12 mm. The impairment in the amplitude of the unconditioned response after cerebellar lesions more closely approximated the impairment in the amplitude of the conditioned response when the force-generating properties of the conditioned and unconditioned stimuli were equated. It was hypothesized, therefore, that one reason why conditioned responses are so easily disrupted by cerebellar lesions is because they are of low force and not simply because they are learned.It was proposed that the two peaks of acceleration that characterize the conditioned response represent the function of two distinct anatomical systems. The first, a short-latency system, initiates the response and is most likely mediated by circuits that traverse the pontomedullary reticular formation. The second, a longer-latency system, amplifies response amplitude and its neural basis remains to be elucidated. The two components of the conditioned response may reflect two sequential bursts of activity in the accessory abducens nucleus, the principal site of the motoneurons for the retractor bulbi muscle, or may reflect the synergistic activity of the accessory abducens nucleus and the motor nuclei of the other extraocular muscles. It was concluded that the vulnerability of the second component of the conditioned response to cerebellar damage reflects an important role for the cerebellum in modulating the degree to which long-latency neural systems contribute to the ongoing performance of learned and unlearned behaviors.

Effects of modulating tone frequency, intensity, and duration on the classically conditioned rabbit nictitating membrane response

Theories of conditioning commonly assume that the conditioned stimulus (CS) activates a cascade of internal stimuli that govern the conditioned response (CR) on a moment-by-moment basis. As a means of manipulating the internal stimuli, in the present experiments we conducted delay conditioning using a tone CS of constant intensity and frequency. However, the subjects were tested with tones during which the frequency (Experiment 1) or intensity (Experiment 2) either increased or decreased in a continuous fashion over an 800-msec period. The experiments revealed that the test stimuli dramatically accelerated the recruitment of the CR. That is, both the initiation and peak of the CR occurred several hundred milliseconds earlier than that seen with the constant tone. CR likelihood and CR amplitude showed modest reductions. A third experiment entailed test manipulations of tone duration, which yielded only small changes in the CR’s time course. The results are discussed with respect to real-time mechanisms of classical conditioning and their neural substrates in the encoding of pure tones.

A substituted pyrrolidinone, BMY 21502, and classical conditioning of the nictitating membrane response in young and older rabbits

New Zealand white rabbits (N = 76; 38 at 3 months, 38 at 21–55 months) were classically conditioned for 10 90-trial sessions in the 750-msec delay paradigm using a tone conditioned stimulus (CS) and corneal airpuff unconditioned stimulus (US). Young and older rabbits were divided into groups receiving paired CS-US presentations with 0, 5, or 10 mg/kg of BMY 21502. Unpaired tone and airpuff presentations were given to control groups administered 0 or 5 mg/kg of BMY 21502. Over training sessions, the older BMY-21502-treated rabbits produced a higher percentage of conditioned responses (CRs) and greater CR amplitude than did the vehicle-treated older rabbits. BMY 21502 did not facilitate conditioning in the young rabbits. There were significant age differences in acquisition between the young and older vehicle-treated animals. Although the BMY-21502-treated older rabbits did not achieve the asymptotic level of performance of the young rabbits, BMY 21502 treatment resulted in conditioning for the older rabbits that was similar to that for the younger rabbits.

A nicotinic agonist (GTS-21), eyeblink classical conditioning and nicotinic receptor binding in rabbit brain

The septo-hippocampal cholinergic system is of demonstrated involvement in eyeblink classical conditioning (EBCC). To determine if a nicotinic cholinergic agonist, GTS-21, would facilitate acquisition of EBCC in older rabbits, three doses (0.1, 0.5, 1.0 mg/kg) in sterile saline vehicle and vehicle alone were administered toolder rabbits ( n = 48; mean age= 29.8 months). A control group of vehicle-treated young rabbits ( n = 12; mean age= 3.5 months) was included. Rabbits were conditioned for fifteen 90-trial sessions in the 750 ms delay paradigm with a tone conditioned stimulus and corneal airpuff unconditioned stimulus. Dependent measures of trials to learning criterion, percentage of conditioned responses (CRs) and CR amplitude consistently showed significant improvement in older rabbits treated with 0.5 and 1.0 mg/kg of GTS-21. Acquisition was similar in vehicle-treated young and GTS-treated older rabbits. Vehicle-treated older rabbits conditioned more poorly than vehicle-treated young rabbits. No non-associative learning effects were observed in GTS-21 treated animals. Nicotinic receptor binding was similar in all groups of older rabbits, indicating that GTS-21 administration over a 15-day period did not affect nicotinic receptors. Alzheimer's disease (AD) has been associated with significant loss of nicotinic cholinergic receptors, and patients diagnosed with probable AD are seriously impaired on EBCC. These results demonstrating that the nicotinic agonist, GTS-21, facilitated EBCC in older rabbits suggest that the compound should receive additional investigation for its potential to affect cognition in AD.