Stimulation of the spinal trigeminal nucleus supports classical conditioning of the rabbit's nictitating membrane response.

Acquisition, extinction, and differential conditioning of the rabbit's nictitating membrane response to a tone conditioned stimulus were supported by electrical stimulation of the spatial trigeminal nucleus. Stimulation of the accessory abducens nucleus, the abducens nucleus, and the reticular formation at the level of the spinal trigeminal nucleus supported lower, transient levels of conditioning. The results are discussed in terms of stimulation of sensory inputs to the brainstem and cerebellum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inactivation of the central nucleus of the amygdala abolishes conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response and delays classical conditioning.

The central nucleus (CE) of the amygdala has been gaining attention for its importance in the plasticity underlying conditioned emotional responding. Already known for its role in nictitating membrane response (NMR) reflex facilitation, the CE may also be involved in conditioning-specific reflex modification (CRM)--changes in the NMR to the unconditioned stimulus (US) when tested in the absence of the conditioned stimulus following classical conditioning. To examine the CE's role in acquisition and/or expression of CRM, the authors temporarily inactivated the CE of rabbits (Oryctolagus cuniculus) with muscimol during NMR conditioning and/or during US testing. Results show that CRM was abolished by inactivation during US testing but intact following inactivation during NMR conditioning, suggesting that the CE is involved in CRM expression. Also, inactivation during conditioning delayed the development of conditioned NMRs. These findings show that the CE may act as an output center for expression of emotional responding in one situation (CRM) but is involved in facilitating plasticity in another (NMR conditioning). The authors propose that analysis of CRM may be an important corollary to current models for the treatment of posttraumatic stress disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trigeminal inputs to eyeblink motoneurons in the rabbit

The rabbit nictitating membrane and eyeblink response is widely used in studies of classical conditioning. Eyeblinks involve coordinated activation of the orbicularis oculi motoneurons (OOcVII) and accessory abducens motoneurons (AccVI) which close the external eyelids and nictitating membrane, respectively, and inhibition of levator palpebrae motoneurons (LPIII) whose activity raises the upper eyelid. The identification of blink interneurons that may coordinate these responses is an important step in the analysis of mechanisms supporting eyeblink conditioning as they are likely to receive convergent inputs from circuitry associated with learned as well as unlearned responses. We first investigated the distribution of OOcVII motoneurons in the facial nucleus and LPIII motoneurons in the oculomotor nucleus by retrograde tracing of wheat germ-agglutinated horseradish peroxidase (WGA-HRP) injected into the appropriate muscles. We then used an anterograde tracing method to locate trigeminal and paratrigeminal inputs to OOcVII, to AccVI nucleus, and to LPIII. Injections of WGA-HRP were placed into the principal trigeminal nucleus (Vp) and into all divisions of the spinal trigeminal nucleus. We found an area in Vp and the adjacent rostral parts of pars oralis of the spinal trigeminal nucleus that gave clear projections to OOcVII and AccVI motoneurons and adjacent to LPIII motoneurons in the contralateral oculomotor nucleus. We suggest that neurons in this premotor blink area in rabbits can coordinate learned and reflex blink responses involving the external eyelids and the nictitating membrane. In addition, there are direct projections from the pars interpolaris and pars caudalis of the spinal trigeminal nucleus to the facial nucleus that may mediate short latency responses of the external eyelid orbicularis oculi muscle alone.     

Classical conditioning and conditioning-specific reflex modification of rabbit heart rate as a function of unconditioned stimulus location.

Heart rate conditioning is used as an index of conditioned fear and is important for understanding disorders of anxiety and stress, including post traumatic stress disorder (PTSD). One important feature of PTSD is that patients generalize conditioned fear from danger signals to safety signals especially when the two signals have overlapping features. What has not been determined is whether generalization occurs between unconditioned stimuli with overlapping features. In the current experiment, heart rate conditioning and conditioning-specific reflex modification of rabbit heart rate were examined as a function of two different unconditioned stimulus locations. Heart rate conditioning occurred at identical terminal levels whether electrical stimulation was presented near the eye or on the back. Despite different heart rate response topographies to electrical stimulation at the two locations, conditioning-specific reflex modification was detected near the eye and on the back and appeared to generalize between the locations. Interestingly, only conditioning-specific reflex modification detected on the back persisted for a week after heart rate conditioning. This persistence may be a model for some features of post traumatic stress disorder. Overgeneralization of unconditioned responses to unconditioned stimuli similar to the trauma may also be an important aspect of PTSD modeled here. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Conditioning-specific reflex modification of rabbit (oryctolagus cuniculus) heart rate.

Conditioning-specific reflex modification (CRM) describes changes in rabbit (Oryctolagus cuniculus) nictitating membrane responses (NMR) to an unconditioned stimulus (US) when the US is tested by itself after pairings of tone and electrodermal stimulation. Although CRM has been replicated, it is unclear whether it occurs in response systems other than that of the NMR. The authors report that CRM of rabbit heart rate (HR) can occur following HR conditioning. A US that elicits HR acceleration before conditioning can elicit HR deceleration after conditioning. The rabbits' electrocardiograms showed both HR conditioning and HR CRM were correlated with an increased PQ interval--an index of parasympathetic function mediated by the vagus. The data suggest conditioned HR deceleration can generalize from conditioned stimulus to US as a function of conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response: Generality and nature of the phenomenon.

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus in the absence of a conditioned stimulus. This form of reflex modification suggests that learning modifies the unconditioned reflex pathway, Rabbit (Oryctolagus cuniculus) nictitating membrane responses to 5 intensities and 3 durations of airpuff (AP) or periorbital electrical stimulation (ES) were monitored before and after conditioning. AP tests detected strong CRM after conditioning with ES and modest levels of CRM after conditioning with AP. After conditioning with AP, ES tests failed to detect CRM. After conditioning with a stronger AP, CRM was again detected by AP tests. CRM is a general phenomenon but is more readily detected after training with a relatively aversive stimulus; thus, it may be a function of level of arousal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural unit activity in the trigeminal complex with interpositus or red nucleus inactivation during classical eyeblink conditioning.

During classical conditioning, many neurons in the trigeminal complex of rabbits exhibit activity that is related to the conditioned stimulus (tone), the unconditioned stimulus (airpuff), or to the conditioned response (eyeblink). For these reasons the trigeminal complex has been hypothesized to be a brainstem locus for the neuronal plasticity associated with conditioning. In this experiment, the learning-related activity (unit activity associated with the conditioned response) in the trigeminal is abolished when either the red nucleus or interpositus nucleus of the cerebellum is temporarily inactivated by cooling, but the stimulus-evoked activity is unaffected by cooling. This study and previous results support the suggestion that the learning-related activity seen in the trigeminal is driven by the interpositus by way of the red nucleus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: II. Lateral reticular nucleus stimulation.

Stimulation of mossy fibers arising from the pontine nuclei can be used as a conditioned stimulus (CS) during classical conditioning of the eyelid/nictitating membrane response (NM). In the present experiment we stimulated another source of mossy fibers, the lateral reticular nucleus (LRN), as a CS for NM conditioning. LRN stimulation was an effective CS, resulting in learning, and the conditioned response to LRN stimulation showed normal extinction. Unpaired presentation of CS and US did not result in pseudo-conditioning. Lesions of the cerebellar dentate-interpositus region abolished the conditioned response but left the unconditioned reflex response intact. We suggest that mossy fibers may normally carry CS information to the cerebellum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Connections to cerebellar cortex (Larsell's HVI) in the rabbit: A WGA-HRP study with implications for classical eyeblink conditioning.

Conditioned eyeblink responses are presumably learned in the cerebellum and relayed to motoneurons by way of the red nucleus. Projections from the red nucleus to cerebellar cortex (Larsell's lobule HVI) could be important for shaping temporally adaptive features of the conditioned response. Rabbits that had pipettes containing wheat germ agglutinated horseradish peroxidase (WGA-HRP) implanted unilaterally into HVI showed retrograde labeling of neurons within subregions of the contralateral red nucleus implicated in eyeblink conditioning by lesioning and recording studies. Retrogradely labeled neurons were also observed in the pontine nuclei, inferior olive, and spinal trigeminal nucleus pars oralis. Projections to HVI provide a possible neural substrate for implementing time-derivative computational models of learning in the cerebellum. Time-derivative models are capable of describing the timing and topography of conditioned responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning the unconditioned response: Modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response.

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to a unconditioned stimulus/stimuli (UCS) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit (Oryctolagus cuniculus) nictitating membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or UCS manipulation. CRM occurred after 12 days of CS-UCS pairings but not following unpaired CS/UCS presentations or restraint. CRM survived CS-alone and CS/UCS-unpaired extinction of the conditioned response (CR) but not presentations of the UCS alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reflex facilitation during eyeblink conditioning and subsequent interpositus nucleus inactivation in the rabbit (Orycotolagus cuniculus).

In eyeblink conditioning in the rabbit (Oryctolagus cuniculus), not only is a conditioned response (CR) acquired, but also the original reflex is modified as a function of training. In Experiment 1, by comparing unconditioned responses in unpaired and paired groups, 3 types of reflex facilitation were distinguished. One type was linked to exposure to the unconditioned stimuli (USs) and/or experimental setting. The 2nd type was related to the formation of the memory trace for conditioned eyeblink. The 3rd type was linked to the conditioned stimulus immediately preceding the US in the paired group. In Experiment 2, reversible inactivation of the interpositus nucleus (IPN) abolished the CR and reduced the CR-related reflex facilitation, indicating that the latter depends on the plasticity of the IPN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Codon bias evolution in Drosophila. Population genetics of mutation-selection drift

Reflex cardiovascular responses elicited by noxious oro-facial stimulation are well known but the neural pathways that underlie trigeminal cardiovascular reflex reactions remain to be elucidated. In previous studies, we have shown that noxious electrical stimulation of the mandibular incisor in the anesthetized rat elicits increases in mean arterial blood pressure and heart rate (Allen, G.V., Barbrick, B. and Esser, M.J., Trigeminal parabrachial connections: possible pathway for nociception-induced cardiovascular reflex responses, Brain Res., 715 (1996) 125-135). In this study, microinjections of the presynaptic blocker, cobalt chloride, or the anesthetic agent, lidocaine, were made into selected brainstem sites to identify neural pathways that are involved in mediation of the reflex pressor responses. Ipsilateral and bilateral injections of chemical blocker into the dorsomedial spinal trigeminal nucleus, pars caudalis, lateral parabrachial nucleus and the rostral ventral lateral medulla/caudal A5 region attenuated the reflex cardiovascular response. Bilateral injections of cobalt chloride into the dorsomedial subnucleus caudalis resulted in 70-100% attenuation of the reflex pressor response. Bilateral injections of cobalt chloride and/or lidocaine into the lateral parabrachial nucleus or the rostral ventral lateral medulla/A5 region resulted in 43-57% and 44-100% attenuation of the reflex pressor response, respectively. There were no significant differences in the degree or duration of attenuation of the reflex pressor responses produced by cobalt chloride compared to that produced by lidocaine injections. The reflex pressor responses usually returned to baseline levels approximately 60 min following injection of the chemical blocker substance. The results indicate that noxious electrical stimulation of the mandibular incisor elicits a reflex increase in mean arterial blood pressure which is initially mediated in the dorsomedial spinal trigeminal nucleus, pars caudalis and is subsequently mediated in the lateral parabrachial nucleus and the rostral ventral lateral medulla/caudal A5 region.     

Effects of amygdala lesions on reflex facilitation and conditioned response acquisition during nictitating membrane response conditioning in rabbit.

Demonstrated that large lesions of the amygdala disrupt the maintenance of reflex facilitation of the unconditioned nictitating membrane (NM) response and slow the acquisition of conditioned NM responses in rabbits. Before behavioral training, the central nucleus of the amygdala and adjacent areas were lesioned electrolytically. In Exp 1, the lesioned animals exhibited no reflex facilitation of the unconditioned NM response at conditioned stimulus (CS)–unconditioned stimulus (UCS) intervals of 125–8,000 ms. In Exps 2 and 3, in which 1 CS–UCS interval (500 ms) was used, the lesions disrupted the maintenance of reflex facilitation but did not alter the facilitation exhibited in the 1st block of training. The lesions retarded the acquisition of conditioned NM responses when the 1,000-Hz tone CS intensity was 65 dB, but not when the intensity was 85 dB. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypoglycemic conditioned reflex in rats: Preliminary study of its mechanism.

Conducted an experiment with female Wistar rats implanted in the left carotid artery. A conditioned reflex was established after a series of reinforcements in which an insulin injection (unconditioned stimulus) was associated with the sound of a bell (conditioned stimulus). The hypoglycemic conditioned response was statistically similar to that of insulin. The latency of the beginning of the hypoglycemic response to insulin was between 4 and 6 min. The latency of the conditioned hypoglycemic response to the conditioning stimulus was about 1 min. Blood extracted from a conditioned S during the test of conditioning produced a hypoglycemic effect when injected into a nonconditioned receptor S. It is concluded that a nervous mechanism was involved in eliciting the hypoglycemic response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Elicitation, modification, and conditioning of the rabbit nictitating membrane response by electrical stimulation in the spinal trigeminal nucleus, inferior olive, interpositus nucleus, and red nucleus.

Elicitation of responses by electrical brain stimulation (EBS) was related to the synaptic distance of the target nucleus from the accessory abducens. Specifically, responses to EBS in the spinal trigeminal nucleus (TRIG) and red nucleus (RN) increased as a positive function of stimulation parameters. Responding to EBS in the interpositus nucleus (IP) was lower, and responding to EBS in the inferior olive (IO) was negligible. EBS in the TRIG, IP, and RN nuclei was then paired with a tone conditioned stimulus (CS). The CS modified responses for EBS in RN and TRIG but not IP. CS-EBS pairings yielded conditioned response (CR) acquisition, in which Groups TRIG, IP, and RN reached asymptotes of 90%, 70%, and 43% CRs, respectively. Thus, contrary to previous findings, EBS in the efferent pathway can support CR acquisition. The results are discussed with respect to the role of projections from the RN to the cerebellar cortex and the TRIG nucleus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning-specific modification of the rabbit's unconditioned nictitating membrane response.

Robust classical conditioning modifies responding to the unconditioned stimulus (US) in the absence of the conditioned stimulus (CS), a phenomenon the researchers called conditioning-specific reflex modification. Unconditioned responses (URs) to periorbital stimulation varying in intensity and duration were assessed before and after 1, 3, or 6 days of paired, explicitly unpaired, or no presentations of tone and electrical stimulation. After 3 days of pairings, conditioned responding (CRs) reached 94%, and there was an increase in latency to the peak of URs. The peak latency increase was replicated in a 2nd experiment where rabbits reached asymptotic conditioning during 6 days of pairings. There was also a conditioning-specific increase in the amplitude of URs. There were no UR changes as a function of low level of CRs following 1 day of pairings. Data suggest that there are learning-specific changes in pathways mediating the US/UR, as well as in those mediating the CS/CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of Claustrum in Pavlovian Heart Rate Conditioning in the Rabbit (Oryctolagus cuniculus) : Anatomical, Electrophysiological, and Lesion Studies.

The role of the claustrum in Pavlovian heart rate (HR) conditioning was studied in the rabbit (Oryctolagus cuniculus) by (a) mapping claustral projections to the prefrontal cortex (PFC), (b) recording claustral single-unit discharge to sensory stimulation and conditioning stimuli during HR conditioning, and (c) assessing the effects of claustral damage on HR conditioning. Contralateral and ipsilateral claustral projections to the PFC were found. Claustral cells responded to nonsignal stimulation with increased discharge and also showed conditioned stimulus-evoked increases in discharge during Pavlovian HR conditioning. Moreover, claustral lesions diminished the magnitude of the HR-conditioned response without affecting the cardiac-orienting response to the conditioned stimulus or the cardiac-unconditioning response to the unconditioned stimulus, suggesting a role for the claustrum in associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning-specific reflex modification of the rabbit's nictitating membrane response and heart rate: Behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder.

Interest in classical conditioning is usually focused on anticipatory responses to a stimulus associated with a significant event, and it is assumed that responses to the event itself are reflexive, involuntary, and relatively invariant. However, there is compelling evidence that both the rabbit nictitating membrane response (NMR) and heart rate response (HR), well-known reflexive reactions to aversive events, can change quite dramatically as a function of learning when measured in the absence of the conditioned stimulus. In the case of NMR conditioning, a simple blink is transformed into a larger and more complex response. For HR conditioning, reflexive heart rate acceleration can actually change to heart rate deceleration. In both cases, the reflex comes to resemble the conditioned response and follows some of the same behavioral laws. This change in response to the aversive event itself or weaker forms of that event is called conditioning-specific reflex modification (CRM). CRM may force us to reevaluate the behavioral and neural consequences of classical conditioning and may have important consequences for the treatment of conditions such as posttraumatic stress disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tone-induced changes in excitability of abducens motoneurons and of the reflex path of nictitating membrane response in rabbit (Oryctolagus cuniculus).

Tested excitability of the reflex nictitating membrane (NM) response to air puff and of the abducens motoneurons (final common path) to direct electrical stimulation (measured as amplitude of the evoked NM response) in 16 New Zealand albino rabbits at various times after onset and offset of a 350-msec tone. Excitability to air puff showed a substantial increase during tone on and a gradual decrease following tone off, in agreement with J. R. Ison and D. W. Leonard (see record 1971-22356-001). Excitability of motoneurons showed a similar marked increase during tone on, a transient decrease immediately following tone off, and then a gradual decrease. It is suggested that these excitability changes, which parallel closely the interstimulus-interval conditionability function reported by I. Gormezano (1966) for the same preparation, may provide an independent measure of the "molar stimulus trace." Excitability of abducens motoneurons tested in the intertrial intervals during subsequent tone-air-puff conditioning showed no consistent changes. Surprisingly, Ss given tone-abducens nucleus shock testing developed conditioned responses. In subsequent conditioning, using standard tone-air-puff training, they showed 85% savings in acquisition relative to nonstimulated controls. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reflex conditioning in a spinal man.

A 40-yr-old man with a completely transected spinal cord and a spastic neurogenic bladder was conditioned to void upon the presentation of an external stimulus. A classical conditioning paradigm was employed in which strong abdominal shock (UCS) was paired with an initially neutral mild electrical stimulation of the thigh (CS). After the pairing trials, a reliable conditioned response of urination was elicited by the CS alone. The conditioned response did not extinguish over time, and the procedure left the bladder with clinically safe residual amounts of urine. Practical implications of the conditioning technique for the treatment of spastic neurogenic bladder conditions in spinally injured patients are discussed, as is the theoretical significance of conditioning at the reflex level in the absence of cortical involvement. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)