Saccular influence on the otolith-spinal reflex and posture during sudden falls of the cat

We made intradendritic recordings in Purkinje cells (n = 164) from parasaggital slices of cerebellar lobule HVI obtained from rabbits given paired presentations of tone and periorbital electrical stimulation (classical conditioning, n = 27) or explicitly unpaired presentations of tone and periorbital stimulation (control, n = 16). Purkinje cell dendritic membrane excitability, assessed by the current required to elicit local dendritic calcium spikes, increased significantly in slices from animals that received classical conditioning. In contrast, membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in slices from animals given paired or explicitly unpaired stimulus presentations. The location of cells with low thresholds for local dendritic calcium spikes suggested that there are specific sites for learning-related changes within lobule HVI. These areas may correspond to learning "microzones" and are consistent with locations of learning-related in vivo changes in Purkinje cell activity. Application of 4-aminopyridine, an antagonist of the rapidly inactivating potassium current IA, reduced the threshold for dendritic spikes in slices from naive animals to levels found in slices from trained animals. In cells where thresholds for eliciting parallel fiber-stimulated Purkinje cell excitatory postsynaptic potentials (EPSPs) were measured, levels of parallel fiber stimulation required to elicit a 6-mV EPSP as well as a 4-mV EPSP (n = 30) and a Purkinje cell spike (n = 56) were found to be significantly lower in slices from paired animals than unpaired controls. A classical conditioning procedure was simulated in slices of lobule HVI by pairing a brief, high-frequency train of parallel fiber stimulation (8 pulses, 100 Hz) with a brief, lower frequency train of climbing fiber stimulation (3 pulses, 20 Hz) to the same Purkinje cell. Following paired stimulation of the parallel and climbing fibers, Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (-24%) in cells (n = 12) from animals given unpaired stimulus presentations but to a far less extent (-9%) in cells (n = 20) from animals given in vivo paired training. Whereas 92% of cells from unpaired animals showed pairing-specific depression, 50% of cells from paired animals showed no depression and in several cases showed potentiation. Our data establish that there are localized learning-specific changes in membrane and synaptic excitability of Purkinje cells in rabbit lobule HVI that can be detected in slices 24 h after classical conditioning. Long-term changes within Purkinje cells that effect this enhanced excitability may occlude pairing-specific long-term depression.     

The vigor of metaphor in clinical practice

Multiple- and single-unit neuronal activities were recorded from cerebellar cortex (Larsell's lobule HVI and adjacent ansiform cortex) and the cerebellar interpositus nucleus during forward (CS-US), backward (US-CS), and explicitly unpaired classical eyeblink conditioning in several rabbits. Whereas learning-related activity was observed in the interpositus nucleus only during forward pairing of the conditioning stimuli, a variety of patterns of learning-related neuronal firings were observed in cerebellar cortex during forward, backward, and even unpaired presentations of the conditioning stimuli. These data suggest that the cerebellar cortex and the deep cerebellar nuclei play different roles during classical eyeblink conditioning.     

Cerebellar stimulation as an unconditioned stimulus in classical conditioning.

Implanted rabbits with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone CS, produced learning comparable to that seen with peripheral unconditioned stimulus/stimuli (UCS). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS–UCS trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS–UCS preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning increases membrane-bound protein kinase C in rabbit cerebellum

We examined membrane-bound protein kinase C (PKC) in the cerebellum of rabbits given paired presentations of a tone conditioned stimulus (CS) that co-terminated with a periocular electrical stimulation unconditioned stimulus (US) or unpaired presentations of the CS and US or restraint in the experimental context. PKC activation was measured by quantitative film autoradiography of [3H]phorbol 12,13-dibutyrate ([3H]PBt2) binding in the molecular and granule cells layers of lobule HVI, anterior vermis and Crus I, and in the dentate/interpositus nuclei. There was a statistically significant increase in [3H]PBt2 binding within the molecular layer of lobule HVI in rabbits given paired training relative to controls. The results indicate PKC activation in lobule HVI may be important in acquisition of conditioned eyeblink responses.     

Impaired classical eyeblink conditioning in cerebellar-lesioned and Purkinje cell degeneration (pcd) mutant mice

Converging lines of evidence from rabbits, rats, and humans argue for the crucial involvement of the cerebellum in classical conditioning of the eyeblink/nictitating membrane response in mammals. For example, selective lesions (permanent or reversible) of the cerebellum block both acquisition and retention of eyeblink conditioning. Correspondingly, electrophysiological and brain-imaging studies indicate learning-related plasticity in the cerebellum. The involvement of the cerebellum in eyeblink conditioning is also supported by stimulation studies showing that direct stimulation of the two major afferents to the cerebellum (the mossy fibers emanating from the pontine nucleus and climbing fibers originating from the inferior olive) can substitute for the peripheral conditioned stimulus (CS) and unconditioned stimulus (US), respectively, to yield normal behavioral learning. In the present study, we examined the relative contribution of the cerebellar cortex versus deep nuclei (specifically the interpositus nucleus) in eyeblink learning by using mutant mice deficient of Purkinje cells, the exclusive output neurons of the cerebellar cortex. We report that Purkinje cell degeneration (pcd) mice exhibit a profound impairment in the acquisition of delay eyeblink conditioning in comparison with their wild-type littermates. Nevertheless, the pcd animals did acquire a subnormal level of conditioned eyeblink responses. In contrast, wild-type mice with lesions of the interpositus nucleus were completely unable to learn the conditioned eyeblink response. These results suggest that both cerebellar cortex and deep nuclei are important for normal eyeblink conditioning.     

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)     

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)     

Eyeblink conditioning leads to fewer synapses in the rabbit cerebellar cortex.

Eyeblink conditioning involves the pairing of a conditioned stimulus (tone) to an aversive unconditioned stimulus (air puff). Although the circuitry that underlies this form of learning is well defined, synaptic changes in these structures have not been fully investigated. This experiment examined synaptic structural plasticity in the cerebellar cortex, a structure that has been found to modulate the acquisition and timing of the conditioned response. Long-term depression of Purkinje cells (PCs) in the cerebellar cortex has been proposed as a mechanism for releasing inhibition of the interpositus nuclei, a structure critical for the formation of the CR. Adult albino rabbits were randomly allocated to either a paired, unpaired, or exposure-only condition. The results showed a significant decrease in the number of excitatory synapses in the outer layer of the cerebellar cortex in the conditioned rabbits compared with controls. This finding suggests that a reduction in the number of excitatory synapses may contribute to the lasting depression of PC activity that is associated with eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of classically conditioned-related activity in the hippocampus is affected by lesions of the cerebellar interpositus nucleus.

Rabbits were first given left cerebellar interpositus nucleus lesions followed by classical nictitating membrane (NM) conditioning using paired presentations of a tone conditioned stimulus (CS) and an air puff unconditioned stimulus (UCS). Multiple-unit hippocampal activity was monitored over the course of training. In rabbits with anterior interpositus lesions, the acquisition of learned responses and significant increases in training-related hippocampal activity were prevented when paired training was given to the left NM but not when training was switched to the right NM. Rabbits with lesions anterior to the interpositus or in surrounding cerebellar regions failed to show deficits in behavioral responding or hippocampal activity. These results indicate that acquisition of conditioning-related activity in the hippocampus depends on an intact interpositus nucleus of the 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)     

Dendritic voltage and calcium-gated channels amplify the variability of postsynaptic responses in a Purkinje cell model

The dendrites of most neurons express several types of voltage and Ca2+-gated channels. These ionic channels can be activated by subthreshold synaptic input, but the functional role of such activations in vivo is unclear. The interaction between dendritic channels and synaptic background input as it occurs in vivo was studied in a realistic computer model of a cerebellar Purkinje cell. It previously was shown using this model that dendritic Ca2+ channels amplify the somatic response to synchronous excitatory inputs. In this study, it is shown that dendritic ion channels also increased the somatic membrane potential fluctuations generated by the background input. This amplification caused a highly variable somatic excitatory postsynaptic potential (EPSP) in response to a synchronous excitatory input. The variability scaled with the size of the response in the model with excitable dendrite, resulting in an almost constant coefficient of variation, whereas in a passive model the membrane potential fluctuations simply added onto the EPSP. Although the EPSP amplitude in the active dendrite model was quite variable for different patterns of background input, it was insensitive to changes in the timing of the synchronous input by a few milliseconds. This effect was explained by slow changes in dendritic excitability. This excitability was determined by how the background input affected the dendritic membrane potentials in the preceding 10-20 ms, causing changes in activation of voltage and Ca2+-gated channels. The most important model variables determining the excitability at the time of a synchronous input were the Ca2+-activation of K+ channels and the inhibitory synaptic conductance, although many other model variables could be influential for particular background patterns. Experimental evidence for the amplification of postsynaptic variability by active dendrites is discussed. The amplification of the variability of EPSPs has important functional consequences in general and for cerebellar Purkinje cells specifically. Subthreshold, background input has a much larger effect on the responses to coherent input of neurons with active dendrites compared with passive dendrites because it can change the effective threshold for firing. This gives neurons with dendritic calcium channels an increased information processing capacity and provides the Purkinje cell with a gating function.     

Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus.

Stimulating electrodes were implanted in rabbit cerebellum, providing an electrical conditioned stimulus (CS) activating cortical parallel fibers and thence Purkinje and other cells, and an electrical unconditioned stimulus (US) activating underlying white matter and eliciting unconditioned responses. Paired CS-US presentations led to the development of conditioned responses, which showed extinction following CS-alone trials and reacquisition with significant savings on reinstatement of paired trials. Increased local excitability as a result of paired training (but not following unpaired stimulus presentations) was observed in cerebellar cortex, as manifested in substantial decreases in CS threshold for response elicitation in all subjects. This preparation offers a model for the study of plastic neuronal interactions within cerebellar networks critically involved in associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related deficits in retention of the classically conditioned nictitating membrane response in rabbits.

Young and aged rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS) for 18 consecutive days. Rabbits were then returned to their home cages for a 90-day period in which they received no further conditioning, but they were handled daily. On Day 91 they underwent retention testing during which the CS alone was presented 20 times. This was immediately followed by reacquisition in which the CS and UCS were again paired for 100 trials. Reacquisition was repeated on the following day. As in previous studies, aged rabbits acquired the conditioned response (CR) more slowly than young rabbits; however, by the end of acquisition, both groups reached similar asymptotic levels. Retention of the CR was significantly lower for aged than young rabbits. Reacquisition was also retarded in aged vs young rabbits. Nonassociative factors, such as sensitivity to the stimuli or general health, could not account for these differences. Data are discussed in terms of using retention of the conditioned eyeblink response as a model system for studying age-related memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Purkinje Cell Loss by OX7-Saporin Impairs Excitatory and Inhibitory Eyeblink Conditioning.

Cerebellar cortical contributions to eyeblink conditioned excitation have been examined extensively. In contrast, very little evidence exists concerning the role of the cerebellar cortex in eyeblink conditioned inhibition. In the current study, rats were given intraventricular infusions of the immunotoxin OX7-saporin to selectively destroy Purkinje cells throughout the cerebellar cortex following excitatory conditioning. After a 2-week postinfusion period, the rats were given reacquisition training. After reacquiring excitatory conditioning, the rats were trained in a feature-negative discrimination procedure to establish conditioned inhibition. Rats treated with OX7-saporin showed impaired reacquisition of excitatory conditioning and acquisition of conditioned inhibition. The results suggest that Purkinje cells play important, but different, roles in conditioned excitation and inhibition in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanism of the radiation-protective effect of indralin

Output from the interpositus nucleus can inhibit the inferior olive, probably via the GABA-ergic nucleo-olivary pathway. It has been suggested that the function of this inhibition might be to regulate synaptic plasticity resulting from parallel fibre/climbing fibre interaction in cerebellar Purkinje cells, by providing negative feedback information to the olive. Thus, when a learned response, generated by the interpositus nucleus, reaches a sufficient amplitude, the olive would be inhibited and further learning blocked. This suggestion was tested in a classical conditioning paradigm. Decerebrate ferrets were trained using electrical skin stimulation of the forelimb as the conditioned stimulus (CS) and periorbital stimulation as the unconditioned stimulus (US). Climbing fibre responses evoked in Purkinje cells by the US were recorded as surface field potentials in the part of the c3 zone controlling eyeblink. It was found that the CS did not inhibit the olive at the beginning of training, but when conditioned responses were large, the olive was inhibited by the CS in some animals. After a number of unpaired CS presentations, which caused extinction of the conditioned response, the inhibition disappeared. The size of individual conditioned responses correlated negatively with the size of the climbing fibre responses evoked by the US. Climbing fibre responses evoked by direct stimulation of the olive were also inhibited. It was concluded that cerebellar output during performance of a conditioned response inhibits the inferior olive. The results thus support the hypothesis of a cerebellar locus of conditioning and are consistent with the proposed role of cerebello-olivary inhibition.     

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: I. Pontine nuclei and middle cerebellar peduncle stimulation.

The nictitating membrane/eyelid responses of 18 rabbits were classically conditioned using cerebellar mossy-fiber stimulation as a conditioned stimulus (CS) and air puff as an unconditioned stimulus (US). The dorsolateral, lateral, and medial pontine nuclei and the middle cerebellar penduncle were effective stimulation-CS sites for training. In one group of rabbits, robust conditioned eyelid responses were produced with paired trials and subsequently extinguished with CS-alone and explicitly unpaired presentation of the CS and US. In a second group of rabbits, no conditioned responses were evident for 4 days of unpaired CS and US presentations. Conditioned responses did develop, however, after paired training was begun. Lesions of the interpositus nucleus of the cerebellum completely abolished the conditioned responses of a third group of rabbits overtrained with the mossy-fiber CS and air-puff US. Results support studies that have demonstrated that the cerebellum is critically involved in acquisition and retention of simple learned responses and theories of cerebellar function which have proposed that mossy fibers supply critical "learning" input to the cerebellum for acquisition and retention of motor skills. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired eyeblink conditioning in 78kDa-glucose regulated protein (GRP78)/immunoglobulin binding protein (BiP) conditional knockout mice.

Evidence grows that the cerebellum and its associated circuitry are the essential neural substrates for standard delay classical eyeblink conditioning. To further investigate the relative roles of the cerebellar cortex and nuclei in eyeblink conditioning, a novel mouse model with Purkinje cell atrophy was studied. The 78kDa-glucose regulated protein, a chaperone molecule, was knocked out leading to postnatal Purkinje cell degeneration (Wang et al., 2010), and standard delay eyeblink conditioning was performed in the conditional knockout mice. Learning was impaired, yet not completely prevented. Histological studies showed a reduction in the cell number and the size of the anterior interpositus nucleus. When the anterior interpositus nucleus was lesioned bilaterally, eyeblink conditioning was completely prevented. The important roles of both cerebellar cortex and AIP nucleus in eyeblink conditioning were seen. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Synaptic enhancement and enhanced excitability in presynaptic and postsynaptic neurons in the conditioned stimulus pathway of Hermissenda

Identified type A photoreceptors of Hermissenda express differential effects of classical conditioning. Lateral type A photoreceptors exhibit an increase in excitability to both the conditioned stimulus (CS; light) and extrinsic current. In contrast, medial type A photoreceptors do not express enhanced excitability, but do show enhancement of the medial B to medial A synaptic connection. Therefore, both enhanced excitability and changes in synaptic strength may contribute to long-term plasticity underlying classical conditioning. The activation of protein kinase C (PKC) is involved in the induction of enhanced excitability of identified type B photoreceptors produced by one-trial conditioning and the expression of enhanced excitability in B photoreceptors after multitrial classical conditioning. We have examined a possible role for persistent kinase activity in the expression of enhanced excitability in lateral type A photoreceptors and enhancement of the medial B to medial type A synaptic connection after classical conditioning. Injection of the PKC inhibitor peptide PKC(19-36) into medial type B photoreceptors of conditioned animals did not significantly change the amplitude of medial A IPSPs elicited by single spikes in the medial B photoreceptor. Injections of PKC(19-36) into medial B photoreceptors of pseudorandom controls also did not significantly change the amplitude of IPSPs recorded from the medial A photoreceptor. In contrast, spikes elicited by extrinsic current in lateral type A photoreceptors of conditioned animals were significantly reduced in frequency after intracellular injection of PKC(19-36) as compared with pseudorandom controls. Injection of the noninhibitory analog peptide [glu27]PKC(19-36) did not affect excitability. Thus, enhanced excitability in the lateral A photoreceptor of conditioned animals seems to be influenced, in part, by a constitutively active kinase or a persistent kinase activator, whereas synaptic enhancement of the connection between the medial B and medial A photoreceptors of conditioned animals may involve a different mechanism.     

Galanin messenger RNA during postnatal development of the rat brain: expression patterns in Purkinje cells differentiate anterior and posterior lobes of cerebellum

Following our initial mapping of preprogalanin messenger RNA in adult brain and its presence in a subpopulation of cerebellar Purkinje neurons [Ryan M. C. and Gundlach A. C. (1996) Neuroscience 70, 709-728], the present study examined the ontogenic expression of preprogalanin messenger RNA in the postnatal rat brain focussing on the Purkinje cells of the cerebellar cortex. Using in situ hybridization histochemistry, preprogalanin messenger RNA was detected in the developing forebrain and hindbrain from postnatal day 4 to day 60 (adult). On postnatal day 4 very light hybridization signal (labelling) was observed in cells of a number of nuclei including the central amygdaloid nucleus, the medial preoptic area, paraventricular nucleus and dorsomedial hypothalamic nucleus of the forebrain while lightly-labelled cells were detected in neurons of the nucleus of the solitary tract and locus coeruleus of the hindbrain. Hybridization signal was not apparent in other nuclei until later, with positively-labelled neurons first apparent in the dorsal cochlear nucleus at postnatal day 21. The abundance of preprogalanin messenger RNA-positive neurons and the intensity of the hybridization signal increased, in most regions, until postnatal day 28 when labelling resembled that of the mature rat. Preprogalanin messenger RNA was first detected in the cerebellum on postnatal day 10 only in Purkinje cells of lobule 10 of the posterior vermis and increased in distribution throughout Purkinje cell layers of the entire cerebellar cortex by postnatal day 13. The intensity of hybridization signal in Purkinje cells varied between lobules, with Purkinje cells in lobule 10 displaying a moderate to heavy degree of labelling, while lobules 6-9 and the more posterior lobules of the hemisphere including crus 2 of the ansiform lobule, the paramedian lobule and the copula pyramis, displayed only light labelling. The intensity of labelling in the anterior vermis and the remaining lobules of the hemisphere including crus 1 of the ansiform lobule, the simple lobule, the paraflocculus and the flocculus, was homogeneously weak. By postnatal day 21, Purkinje cell labelling reached maximum intensity in all lobules. Regional differences were still apparent, however, with labelling in the posterior vermis and hemisphere ranging from moderate to heavy, with only light to moderate labelling detected in the anterior vermis. The intensity of labelling in the posterior vermis and most lobules of the hemisphere was similar from postnatal day 21 to adulthood, while, in the anterior vermis, crus 1 of the ansiform lobule and the simple lobule, the intensity of hybridization decreased slightly by postnatal day 28 and was completely absent in Purkinje cells of the adult rat. Differential expression of preprogalanin messenger RNA in Purkinje cells of the developing rat cerebellum and transient expression in certain lobules suggests that galanin gene products may have a role in both the developing and mature rat brain and that galanin gene expression may represent a useful marker for differentiating the anterior and posterior cerebellar lobes.     

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)