Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR).

Exploration of cerebellar-dependent associative learning in schizophrenia: effects of varying and shifting interstimulus interval on eyeblink conditioning.

Eyeblink conditioning abnormalities have been reported in schizophrenia, but the extent to which these anomalies are evident across a range of delay intervals (i.e., interstimulus intervals; ISIs) is unknown.

Evaluation of bidirectional interstimulus interval (ISI) shift in auditory delay eye-blink conditioning in healthy humans.

Delay eye-blink conditioning is an associative learning task that can be utilized to probe the functional integrity of the cerebellum and related neural circuits. Typically, a single interstimulus interval (ISI) is utilized, and the amplitude of the conditioned response (CR) is the primary dependent variable. To study the timing of the CR, an ISI shift can be introduced (e.

Cerebellar-dependent eyeblink conditioning deficits in schizophrenia spectrum disorders.

Accumulating evidence suggests that abnormalities in neural circuitry and timing associated with the cerebellum may play a role in the pathophysiology of schizophrenia. Schizotypal personality disorder (SPD) may be genetically linked to schizophrenia, but individuals with SPD are freer from potential research confounds and may therefore offer insight into psychophysiological correlates of schizophrenia. The present study employed a delay eyeblink conditioning (EBC) procedure to examine cerebellar-dependent learning in schizophrenia, SPD, and healthy control subjects (n = 18 per group) who were matched for age and gender.

MK-801 administration during neonatal ethanol withdrawal attenuates interpositus cell loss and juvenile eyeblink conditioning deficits.

Binge-level doses of ethanol have been demonstrated to severely disrupt the cerebellum and cerebellum-dependent tasks when administered to rodent subjects during the early postnatal period. N-methyl-d-aspartic acid (NMDA) receptor-mediated excitotoxicity associated with ethanol withdrawal has been implicated as a significant component contributing to neurotoxic effects resulting from early ethanol exposure, and studies using MK-801 (dizocilpine) have reported protection from ethanol-induced damage. The present study examined whether the administration of MK-801 during ethanol withdrawal would ameliorate ethanol-associated cell death in the interpositus nucleus of the cerebellum and behavioral deficits in a cerebellar dependent task.

Conditioned fear in adult rats is facilitated by the prior acquisition of a classically conditioned motor response.

Early in eyeblink classical conditioning, amygdala-dependent fear responding is reported to facilitate acquisition of the cerebellar-dependent eyeblink conditioned response (CR), in accord with the two-process model of conditioning (Konorski, 1967). In the current study, we predicted that the conditioned fear (e.g.

Comparison of auditory and visual conditioning stimuli in delay eyeblink conditioning in healthy young adults.

Classical eyeblink conditioning (EBC) has been widely used to probe cerebellar function in humans and nonhuman mammals. Although the neural pathways governing behavior in this task are well understood and fairly discrete, it remains unclear in the human literature how conditioned stimuli (CSs) of different modalities (e.g.

Eye-blink conditioning deficits indicate temporal processing abnormalities in schizophrenia.

Theoretical models suggest that symptoms of schizophrenia may be due to a dysfunctional modulatory system associated with the cerebellum. Although it has long been known that the cerebellum plays a critical role in associative learning and motor timing, recent evidence suggests that it also plays a role in nonmotor psychological processes. Indeed, cerebellar anomalies in schizophrenia have been linked to cognitive dysfunction and poor long-term outcome.

Secretin effects on cerebellar-dependent motor learning in schizophrenia.

Objective: Pervasive cognitive deficits in schizophrenia are a major cause of disability among individuals with the disorder. One such deficit is the loss of effective associative learning, which is readily assessed via eye-blink conditioning procedures. The authors examined the efficacy of secretin, a hormonal agonist for the prototype group B G-protein-coupled receptors, in ameliorating eye-blink conditioning deficits in schizophrenia patients.

Eyeblink conditioning during an interstimulus interval switch in rabbits (Oryctolagus cuniculus) using picrotoxin to disrupt cerebellar cortical input to the interpositus nucleus.

The role of the cerebellar cortex in eyeblink classical conditioning remains unclear. Experimental manipulations that disrupt the normal function impair learning to various degrees, and task parameters may be important factors in determining the severity of impairment. This study examined the role of cerebellar cortex in eyeblink conditioning under conditioned stimulus?unconditioned stimulus intervals known to be optimal or nonoptimal for learning.

Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction.

Objectives: Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD.

Methods: Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls.

Associative and non-associative blinking in classically conditioned adult rats.

Over the last several years, a growing number of investigators have begun using the rat in classical eyeblink conditioning experiments, yet relatively few parametric studies have been done to examine the nature of conditioning in this species. We report here a parametric analysis of classical eyeblink conditioning in the adult rat using two conditioned stimulus (CS) modalities (light or tone) and three interstimulus intervals (ISI; 280, 580, or 880 ms). Rats trained at the shortest ISI generated the highest percentage of conditioned eyeblink responses (CRs) by the end of training.

Cerebellum volume and eyeblink conditioning in schizophrenia.

Although accumulating evidence suggests that cerebellar abnormalities may be linked to the symptoms and course of schizophrenia, few studies have related structural and functional indices of cerebellar integrity. The present study examined the relationship between the volume of specific subregions of the cerebellum and cerebellar function, as measured by eyeblink conditioning (EBC). Nine individuals with schizophrenia and six healthy comparison participants completed structural magnetic resonance imaging of the brain and a delay EBC procedure.

Hippocampal lesions in rats differentially affect long- and short-trace eyeblink conditioning.

Extensive previous research has implicated the hippocampus as an important structure for the acquisition of trace eyeblink conditioning. Evidence from multiple species and various lesioning methods shows that the disruption of conditioned responding (CR) may be partially dependent on the relative lengths of the conditioned stimulus (CS) period and the trace interval. The present study systematically manipulated the length of the CS and the trace interval while matching the interstimulus intervals (ISI) in rats with or without ibotenic acid hippocampal lesions.

Psychological functions of the cerebellum.

For most of the 20th century, the brain science community held the view that the cerebellum was exclusively involved in motor control functions. Over the past 20 years, this has largely been replaced by the idea that the cerebellum participates in a variety of motor and nonmotor functions and, importantly, may contain neurons that display long- and short-term plasticity, encoding behavioral and cognitive functions. The authors present evidence for the involvement of the cerebellun in motor and nonmotor functions and further suggest that the cerebellum's internal neural architecture and connectivity patterns with other areas of the brain determine the range of functions that the cerebellum participates in.

Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum.

Neonatal maternal separation alters learning and memory. Glucocorticoids also modulate adult learning and memory, and neonatal maternal separation alters forebrain glucocorticoid receptor (GR) concentrations. We used eyeblink classical conditioning to assess the effect of neonatal maternal separation on associative learning.

Cannabis use disrupts eyeblink conditioning: evidence for cannabinoid modulation of cerebellar-dependent learning.

While the cerebellum contains the highest density of cannabinoid receptor (CB1) in the brain, no studies have assessed the effect of exogenous cannabinoids on cerebellar-dependent learning in humans. The current study, therefore, examined the effect of chronic cannabis use on classical eyeblink conditioning (EBC), a cerebellar-mediated task which has been shown to be disrupted in CB1 knockout mice. Chronic cannabis users (24 h abstinence before study; positive THC urine drug test) free of DSM-IV Axis-I or -II disorders, were evaluated.

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities.

Binge-like exposure to ethanol early in development results in neurotoxic impairments throughout the brain, including the cerebellum and brainstem. Rats exposed to ethanol, during a period of time commensurate with the human third trimester, also show deficits in classical eyeblink conditioning (EBC), a cerebellar-dependent associative learning procedure. The relationship between ethanol-mediated EBC deficits and the intensity of the unconditioned stimulus (US) was explored in the current study.

Neuroscience and learning: lessons from studying the involvement of a region of cerebellar cortex in eyeblink classical conditioning.

How the nervous system encodes learning and memory processes has interested researchers for 100 years. Over this span of time, a number of basic neuroscience methods has been developed to explore the relationship between learning and the brain, including brain lesion, stimulation, pharmacology, anatomy, imaging, and recording techniques. In this paper, we summarize how different research approaches can be employed to generate converging data that speak to how structures and systems in the brain are involved in simple associative learning.

Effects of emotional valence and arousal manipulation on eyeblink classical conditioning and autonomic measures.

Using a classical eyeblink conditioning paradigm, we have previously shown that the rate of acquisition of a conditioned response may be manipulated by engaging subjects in background tasks of varying complexity concurrent to conditioning. To further examine the influence of the background environment on conditioning, a picture set designed to elicit emotional responses, the International Affective Picture System (IAPS), was presented to subjects during classical eyeblink conditioning. The results suggest that eyeblink conditioning does appear to be sensitive to contextual manipulations of arousal.

Amygdalar unit activity during three learning tasks: eyeblink classical conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning.

Neural activity in central and basolateral amygdala nuclei (CeA and BLA, respectively) was recorded during delay eyeblink conditioning, Pavlovian fear conditioning, and signaled barpress avoidance. During paired training, the CeA exhibited robust learning-related excitatory activity during all 3 tasks. By contrast, the BLA exhibited minimal activity during eyeblink conditioning, while demonstrating pronounced increases in learning-related excitatory responsiveness during fear conditioning and barpress avoidance.

Purkinje cell activity in the cerebellar anterior lobe after rabbit eyeblink conditioning.

The cerebellar anterior lobe may play a critical role in the execution and proper timing of learned responses. The current study was designed to monitor Purkinje cell activity in the rabbit cerebellar anterior lobe after eyeblink conditioning, and to assess whether Purkinje cells in recording locations may project to the interpositus nucleus. Rabbits were trained in an interstimulus interval discrimination procedure in which one tone signaled a 250-msec conditioned stimulus-unconditioned stimulus (CS-US) interval and a second tone signaled a 750-msec CS-US interval.

The effects of amygdala lesions on hippocampal activity and classical eyeblink conditioning in rats.

The hippocampus and the amygdala have long been associated with memory, emotion, and motivated behaviors. Although the role of these two brain areas in learning a simple, discrete motor response has been well studied, a definitive theory concerning their functions remains elusive. The present experiment involved selective lesions of the central nucleus (CE) or the basolateral nucleus (BA) of the amygdala in rats followed by single-unit analyses of hippocampal CA1 subfield activity during classical eye blink conditioning.

Heart rate reactivity in HAD and LAD rats during Pavlovian fear conditioning.

Recently, we reported that High-Alcohol-Drinking (HAD) rats exhibited selective deficits in active avoidance learning under alcohol-naive conditions, and that administration of moderate doses of alcohol (0.5 and 1.0 g/kg) facilitated learning in these rats (Blankenship et al.