Retention and extinction of delay eyeblink conditioning are modulated by central cannabinoids

Rats administered the cannabinoid agonist WIN55,212-2 or the antagonist SR141716A exhibit marked deficits during acquisition of delay eyeblink conditioning, as noted by Steinmetz and Freeman in an earlier study. However, the effects of these drugs on retention and extinction of eyeblink conditioning have not been assessed. The present study examined the effects of WIN55,212-2 and SR141716A on retention and extinction of delay eyeblink conditioning in rats. Rats were given acquisition training for five daily sessions followed by one session of retention training with subcutaneous administration of 3 mg/kg of WIN55,212-2 or 5 mg/kg of SR141716A and an additional session with the vehicle. Two sessions of extinction training were then given with WIN55,212-2, SR141716A, or vehicle. Retention and extinction were impaired by WIN55,212-2, whereas SR141716A produced no deficits. The extinction deficit in rats given WIN55,212-2 was observed only during the first session, suggesting a specific impairment in short-term plasticity mechanisms. The current results and previous findings indicate that the cannabinoid system modulates cerebellar contributions to acquisition, retention, and extinction of eyeblink conditioning.     

Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning.     

Exploring the theoretical underpinnings of driving whilst influenced by illicit substances

An increasing number of studies are highlighting the alarming proportion of motorists that drive after having consumed illicit drugs. However presently, little attention has focused on the factors that may facilitate drug driving from a criminogenic paradigm. This study evaluated the contribution of deterrence, defiance, and deviance theories on intentions to drug drive to determine factors that might facilitate or reduce this behaviour. A total of 922 individuals completed a questionnaire that assessed frequency of drug use and a variety of perceptions on deterrence, defiance, and deviance constructs. The analysis showed that the defiance constructs (i.e., experiencing feelings of shame and believing in the legitimacy of sanctioning authority) and the deviance constructs (i.e., moral attachment to the norm and having a criminal conviction) were predictive of drug driving intentions. The facets of deterrence theory were not found to be significant predictors. Ultimately, this study illustrates that a range of behavioural and perceptual factors have the capacity to influence decisions to drug drive. As a result, there appears the need to extend the focus of research endeavours beyond legal sanctions to examine other factors that may be utilised to both understand the aetiology of drug driving as well as increase the possibility of compliance with the corresponding legislation.     

Ventral lateral geniculate input to the medial pons is necessary for visual eyeblink conditioning in rats

The conditioned stimulus (CS) pathway that is necessary for visual delay eyeblink conditioning was investigated in the current study. Rats were initially given eyeblink conditioning with stimulation of the ventral nucleus of the lateral geniculate (LGNv) as the CS followed by conditioning with light and tone CSs in separate training phases. Muscimol was infused into the medial pontine nuclei (MPN) after each training phase to examine conditioned response (CR) retention to each CS. The spread of muscimol infusions targeting the MPN was examined with fluorescent muscimol. Muscimol infusions into the MPN resulted in a severe impairment in retention of CRs with the LGNv stimulation and light CSs. A less severe impairment was observed with the tone CS. The results suggest that CS information from the LGNv and light CSs is relayed to the cerebellum through the MPN. Retrograde tracing with fluoro-gold (FG) showed that the LGNv and nucleus of the optic tract have ipsilateral projections to the MPN. Unilateral inputs to the MPN from the LGNv and nucleus of the optic tract may be part of the visual CS pathway that is necessary for visual eyeblink conditioning.The neural substrates of associative motor learning have been studied extensively using eyeblink conditioning (Christian and Thompson 2003; Thompson 2005). Eyeblink conditioning is typically established by pairing a tone or light conditioned stimulus (CS) with an unconditioned stimulus (US) that elicits the eyeblink reflex. An eyeblink conditioned response (CR) emerges over the course of paired training, and the peak of eyelid closure occurs at the onset time of the US. Results from experiments using temporary lesions of the cerebellar deep nuclei or cerebellar cortex indicate that the anterior interpositus nucleus and cerebellar cortex are necessary for acquisition, expression, and extinction of eyeblink conditioning (Krupa et al. 1993; Hardiman et al. 1996; Krupa and Thompson 1997; Garcia and Mauk 1998; Medina et al. 2001; Bao et al. 2002; Freeman et al. 2005a). Blocking cerebellar output with inactivation of the superior cerebellar peduncle, red nucleus, or brainstem motor nuclei selectively blocks CR expression but not acquisition, providing further evidence that learning occurs in the cerebellum (Chapman et al. 1990; Krupa et al. 1993, 1996; Krupa and Thompson 1995).Sensory stimuli from every modality are sent to the pontine nuclei (PN), which receive projections from the lower brainstem, thalamus, and cerebral cortex (Glickstein et al. 1980; Brodal 1981; Mihailoff et al. 1989; Schmahmann and Pandya 1989; Wells et al. 1989; Knowlton et al. 1993; Campolattaro et al. 2007). Neurons in the PN project CS information to the cerebellum via mossy fibers in the middle cerebellar peduncle that synapse on granule cells in the cerebellar cortex and on neurons in the interpositus nucleus (Bloedel and Courville 1981; Brodal 1981; Steinmetz and Sengelaub 1992; Mihailoff 1993). Lesions of the middle cerebellar peduncle impair eyeblink conditioning with auditory, somatosensory, and visual CSs (Lewis et al. 1987). Bilateral electrolytic lesions of the dorsolateral and lateral pontine nuclei (LPN) block retention of CRs to an auditory CS but have no effect on light-elicited CRs (Steinmetz et al. 1987). Inactivation of the contralateral LPN blocks CRs to a tone CS but not to lateral reticular nucleus stimulation in rabbits (Bao et al. 2000). Moreover, stimulation of the LPN or middle cerebellar peduncle is a sufficient CS for eyeblink conditioning (Steinmetz et al. 1986, 1987; Tracy et al. 1998; Bao et al. 2000; Freeman and Rabinak 2004; Freeman et al. 2005b; Campolattaro and Freeman 2008). The findings from the lesion, inactivation, and stimulation studies provide evidence that the PN is the proximal part of the CS pathway for cerebellar learning. These studies also indicate that the LPN is the primary source of auditory CS input to the cerebellum.Only a few studies have examined the visual CS pathway necessary for eyeblink conditioning. The dorsal and ventral divisions of the lateral geniculate nucleus of the thalamus (LGNd, LGNv), pretectal nuclei, visual cortex (VCTX), and superior colliculus (SC) comprise a hypothesized parallel visual CS pathway for eyeblink conditioning (Koutalidis et al. 1988). Combined lesions of all of these visual areas completely block acquisition, lesions of two visual areas produce a partial impairment, and lesions in one visual area do not impair CR acquisition (Koutalidis et al. 1988). Stimulation of the VCTX, SC, and LGNv support eyeblink conditioning, and each of these structures has a direct unilateral projection to the PN that could be important for eyeblink conditioning (Halverson et al. 2009). The lesion and stimulation studies provide evidence that structures in the hypothesized visual CS pathway are independently capable of supporting conditioning. An important aspect of the visual CS pathway proposed in the Koutalidis et al. (1988) study is distributed projections of each visual area to different regions of the PN. The important projections were hypothesized to be from the VCTX to the rostral portion of the PN, from both the SC and pretectal nuclei to the dorsolateral PN, and the LGNv projection to the medial pontine nuclei (MPN) (Koutalidis et al. 1988). Lesions of the VCTX were substituted for LGN lesions in the Koutalidis et al. (1988) study due to technical problems with animal survival. The LGNv projection to the MPN was therefore not examined in their combined lesion group. Stimulation of the anterior pretectal nucleus is not a sufficient CS to support eyeblink conditioning (Campolattaro et al. 2007). The direct PN projection from the VCTX is not necessary for CR retention to a light CS, as lesions do not prevent eyeblink conditioning to a light CS in dogs or monkeys (Hilgard and Marquis 1935, 1936). Moreover, lesions of the entire cerebral cortex do not prevent acquisition or retention of delay eyeblink conditioning to a tone or light CS in rabbits (Oakley and Russell 1972, 1977). The LGNv and SC, therefore, are likely sources of visual input to the PN that is necessary for eyeblink conditioning.The current experiment investigated whether information from the LGNv and a visual CS (light) share similar inputs into the MPN and whether those inputs are different from an auditory CS. The visual projections to the MPN were also investigated with the retrograde tracer fluoro-gold (FG) to identify structures that may be involved with the relay of CS information during eyeblink conditioning. In the conditioning experiment, rats received three phases of training, with each phase consisting of three acquisition sessions followed by a muscimol infusion into the MPN, and then a saline recovery session. Each rat received unilateral stimulation of the LGNv (contralateral to the trained eye) during phase 1 of training followed by either a tone or light CS in phases 2 and 3 (order of stimulus presentation was counterbalanced). One group received LGNv stimulation in phase 1 followed by a light CS in phase 2, and a tone CS in phase 3 (SLT). The other group received the tone CS in phase 2, and light CS in phase 3 (STL).     

Central cannabinoid receptors modulate acquisition of eyeblink conditioning

Delay eyeblink conditioning is established by paired presentations of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex, particularly the molecular layer, contains a high density of cannabinoid receptors (CB1R). The CB1Rs are located on the axon terminals of parallel fibers, stellate cells, and basket cells where they inhibit neurotransmitter release. The present study examined the effects of a CB1R agonist WIN55,212-2 and antagonist SR141716A on the acquisition of delay eyeblink conditioning in rats. Rats were given subcutaneous administration of 1, 2, or 3 mg/kg of WIN55,212-2 or 1, 3, or 5 mg/kg of SR141716A before each day of acquisition training (10 sessions). Dose-dependent impairments in acquisition were found for WIN55,212-2 and SR141716A, with no effects on spontaneous or nonassociative blinking. However, the magnitude of impairment was greater for WIN55,212-2 than SR141716A. Dose-dependent impairments in conditioned blink response (CR) amplitude and timing were found with WIN55,212-2 but not with SR141716A. The findings support the hypothesis that CB1Rs in the cerebellar cortex play an important role in plasticity mechanisms underlying eyeblink conditioning.     

Flexible and inflexible response components: a Stroop study with typewritten output

Two experiments were directed at investigating the relationship between response selection and execution in typewriting, and specifically the extent to which concurrent processing takes place. In a Stroop paradigm adapted from [Logan, G. D., & Zbrodoff, N. J. (1998). Stroop-type interference: Congruity effects in colour naming with typewritten responses. Journal of Experimental Psychology: Human Perception and Performance, 24, 978–992], participants typed the names of colour patches with incongruent, congruent, or neutral distractors presented at various stimulus-onset asynchronies. Experiment 1 showed Stroop interference and facilitation for initial keystroke latencies and errors, contrasting with response durations (a measure of response execution) being unaffected by Stroop manipulation. Experiment 2 showed that all three measures were responsive to time pressure; again, Stroop effects were confined to latencies and errors only. The observation that response duration is both flexible under time pressure and protected from response competition, may imply either that response execution is structurally segregated from earlier processing stages, or that encapsulation develops during the acquisition of typing skills.     

Report of the ACA Ethics Committee: 2006–2007

This report summarizes the activities of the American Counseling Association Ethics Committee during the period from July 1, 2006, through June 30, 2007. Ethics Committee membership, an overview of the mission of the Ethics Committee and goals for 2006–2007, summary data of the complaints filed and the inquiries received, and education activities of the Committee are presented.     

Ontogenetic change in the auditory conditioned stimulus pathway for eyeblink conditioning

Two experiments examined the neural mechanisms underlying the ontogenetic emergence of auditory eyeblink conditioning. Previous studies found that the medial auditory thalamus is necessary for eyeblink conditioning with an auditory conditioned stimulus (CS) in adult rats. In experiment 1, stimulation of the medial auditory thalamus was used as a CS in rat pups trained on postnatal days (P) 17-18, 24-25, or 31-32. All three age groups showed significant acquisition relative to unpaired controls. However, there was an age-related increase in the rate of conditioning. Experiment 2 examined the effect of inactivating the medial auditory thalamus with muscimol on auditory eyeblink conditioning in rats trained on P17-18, 24-25, or 31-32. Rat pups trained on P24-25 and P31-32, but not P17-18, showed a significant reduction in conditioned responses following muscimol infusions. The findings suggest that the thalamic contribution to auditory eyeblink conditioning continues to develop through the first postnatal month.