Cerebellar Contribution Research Articles

Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation.

Cerebellar Contributions to Reach Adaptation and Learning Sensory Consequences of Action

When we use a novel tool, the motor commands may not produce the expected outcome. In healthy individuals, with practice the brain learns to alter the motor commands. This change depends critically on the cerebellum as damage to this structure impairs adaptation. However, it is unclear precisely what the cerebellum contributes to the process of adaptation in human motor learning. Is the cerebellum crucial for learning to associate motor commands with novel sensory consequences, called forward model, or is the cerebellum important for learning to associate sensory goals with novel motor commands, called inverse model? Here, we compared performance of cerebellar patients and healthy controls in a reaching task with a gradual perturbation schedule. This schedule allowed both groups to adapt their motor commands. Following training, we measured two kinds of behavior: in one case, people were presented with reach targets near the direction in which they had trained. The resulting generalization patterns of patients and controls were similar, suggesting comparable inverse models. In the second case, participants reached without a target and reported the location of their hand. In controls, the pattern of change in reported hand location was consistent with simulation results of a forward model that had learned to associate motor commands with new sensory consequences. In patients, this change was significantly smaller. Therefore, in our sample of patients, we observed that while adaptation of motor commands can take place despite cerebellar damage, cerebellar integrity appears critical for learning to predict visual sensory consequences of motor commands.

Consensus paper: pathological role of the cerebellum in autism.

There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

Mechanisms of cerebellar contributions to cognition in humans.

The role of the human cerebellum in cognitive processes is the subject of ongoing debate. On the basis of neuroanatomical findings of closed cerebro-cerebellar loops in monkeys, which originate not only in motor but also in nonmotor regions of the cerebral cortex, this article addresses mechanisms of the involvement of the human cerebellum in two well-studied cognitive domains, executive function, working memory in particular, and associative learning, with special emphasis on the nature of a potential cerebellar contribution to these cognitive processes. The uniform organization of cortico-cerebellar connections suggests parallels in cerebellar information processing in motor- and nonmotor contexts. Taking into account recent models on cerebellar function, it is suggested that the main contribution of the cerebellum to motor as well as to cognitive tasks may be to provide accurate predictions of future sensations, actions, and events. WIREs Cogn Sci 2012, 3:171-184. doi: 10.1002/wcs.1161 For further resources related to this article, please visit the WIREs website.

Examining the genetic and neural components of cognitive flexibility using mice

This commentary summarizes the research presented during the symposium "Examining the genetic and neural components of cognitive flexibility using mice" at the annual meeting of the International Behavioral Neuroscience Society 2011. Research presented includes examining: 1) Corticostriatal networks underlying reversal learning using GluN2B knockout mice, cFos expression, and in vivo electrophysiological recording; 2) Cerebellar contribution to reversal learning using mutants with Purkinje cell loss and in vivo electrochemical recording; 3) Parvalbumin contribution to reversal learning and set-shifting using PLAUR mutants and in vitro recording to examine fast-spiking interneurones; and 4) Alpha 7 nAChR contribution to reversal learning, set-shifting, motivation, and the 'eureka moment' of rule acquisition. It is proposed that these studies revealed more about the neurobiology underlying these behaviors than could be discovered using pharmacological techniques alone. Together, the research presented stressed the importance of exploring the genetic contribution to neuropsychiatric disease and the important role that the mouse, coupled with robust behavioral measures, can play in understanding neurobiology underlying cognitive flexibility.

Volumetric Reduction of Cerebellum Associated with Cognitive, Affective and Behavioral Changes

Back to table of contents Previous article Next article LettersFull AccessVolumetric Reduction of Cerebellum Associated with Cognitive, Affective and Behavioral ChangesRafaela Oliveira da Silva, Elie Cheniaux Jr., and Marco Andre MezzasalmaRafaela Oliveira da SilvaSearch for more papers by this author, Elie Cheniaux Jr.Search for more papers by this author, and Marco Andre MezzasalmaSearch for more papers by this authorPublished Online:1 Apr 2012https://doi.org/10.1176/appi.neuropsych.11060131AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The cerebellum has traditionally been associated to the coordination of motor functions, however there is increasing evidence of a cerebellar contribution in higher cognitive functions.1–4The cerebellar cognitive affective syndrome is clinically characterized by disturbances of executive functions, impairments in spatial cognition, personality changes and language difficulties.5 Since its description, there is a lack of reports of cases with pure cerebellar disorders to address its contribution in cognitive or affective impairments.We report a case of volumetric reduction of cerebellum, with no extracerebellar abnormalities, associated with cognitive impairment and behavior change.Case ReportA 45-year-old male patient presented inappropriate behavior and personality changes: undressing in public places, talking loudly and quickly, and behaving aggressively with his wife. Eight months after the beginning of symptoms, the patient attempted suicide. He started psychiatric treatment but the symptomatology gradually worsened, despite pharmacologic treatment.The patient presented progressive loss of interest, social withdrawal, impairments in intellectual and emotional functioning, impulsive behavior and inability to recover his daily activities. His first psychiatric admission was when he was 52, after physically assaulting his mother.In March 2009, at age of 53 years old the patient was first admitted in our infirmary due to violent behavior. On admission he presented with limited spontaneous conversations and impoverishment of the content of thought, concrete interpretation, hypoprosody, inability to conduct simple calculations, diminished verbal fluency, apathy, blunted affect, facial hypomodulation, hypobulia, decreased psychomotor activity and poor fine motor coordination. His score at the MMSE was 22. The patient remained most of the time in his room, with a childish and impulsive behavior, verbally and physically attacking other inpatients.He had normal hemogram, electrolytes, anti-HIV, VDRL, liver, renal and thyroid functions and vitamin B12. He underwent a MRI with volumetric reduction of cerebellum and enlargement of cerebellar sulci, basal cistern and IV ventricle. MRI showed no structural abnormalities outside the cerebellum.We began quetiapine 600 mg/day, chlorpromazine 100 mg/day and clonazepam 1.5 mg/day, there was noticeable improvement of aggressiveness and impulsivity. The patient was discharged after 60 days of hospitalization. He was evaluated with the CAMCOG battery and scored 53, lower than expected for his age and education with impairments in working memory, verbal fluency and executive functions. Since then, he attends monthly to medical visits and his mental state is stabilized.DiscussionIn 1998 the “cerebellar cognitive affective syndrome” was described and characterized by impairments of executive functions; visual-spatial disorganization and impairment of visual-spatial memory; personality changes and inappropriate behavior; and difficulties with linguistic abilities.5In this case, impairments in executive function, linguistic abilities and personality changes are correlated to the neuropsychological and neuroimaging findings, and are consistent with the diagnosis of “cerebellar cognitive affective syndrome”. With pharmacologic treatment, aggressiveness and impulsivity improved considerably, although the cognitive impairments have remained. Further studies are still needed to elucidate the nature of the cerebellar mediation of cognitive process, their possibly link to motor functions and treatment alternatives to improve the cognitive impairment of these patients.Rio de Janeiro, BrazilReferences1 Leiner HC, Leiner AL, Dow RS: Does the cerebellum contribute to mental skills? Behav Neurosci 1986; 100:443–454Crossref, Medline, Google Scholar2 Schmahmann JD: An emerging concept. The cerebellar contribution to higher function. (Review) Arch Neurol 1991; 48:1178–1187Crossref, Medline, Google Scholar3 Timmann D, Daum I: Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum 2007; 6:159–162Crossref, Medline, Google Scholar4 Schmahmann JD, Weilburg JB, Sherman JC: The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum 2007; 6:254–267Crossref, Medline, Google Scholar5 Schmahmann JD, Sherman JC: The cerebellar cognitive affective syndrome. Brain 1998; 121:561–579Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byCurrent Atherosclerosis Reports, Vol. 19, No. 6 Volume 24Issue 2 Spring 2012Pages E21-E21 Metrics PDF download History Published online 1 April 2012 Published in print 1 April 2012

Isolating a cerebellar contribution to rapid visual attention using transcranial magnetic stimulation

Patient and neuroimaging research have provided increasing support for a role of the posterior-lateral cerebellum in cognition, particularly attention. During rapid serial visual presentation, when two targets are presented in close temporal proximity (<500 ms), accuracy at detecting the second target (T2) suffers. This phenomenon is known as the attentional blink (AB), and in cerebellar lesion patients this effect is exaggerated. Damage to the cerebellum may thus disrupt the use of attentional resources during stimulus processing conditions that are temporally demanding. There are reciprocal connections between the cerebral cortex and the contralateral cerebellum, these connections allow for the possibility that lateralized functions in the cerebral cortex (such as language) remain lateralized in the cerebellum. The purpose of this study was to investigate the temporal characteristics of the cerebellar contribution to the AB and to functionally localize the contribution of the cerebellum to the AB using transcranial magnetic stimulation (TMS). We hypothesized that T2 accuracy would decrease after right cerebellar stimulation when the delay between the first target (T1) and T2 was short (120–400 ms) compared to long (720–960 ms). We used continuous theta burst stimulation (cTBS), a form of TMS, to transiently inhibit a focal population of neurons in the left and right posterior-lateral cerebellum of healthy participants (n = 45). Three groups of participants (n = 15) performed the AB before and after either sham, left, or right cerebellar stimulation. The results of this cTBS study support our hypothesis. During the short delay, participants in the right cTBS group showed a greater AB magnitude compared to both the left and sham cTBS groups (p < 0.05). No difference in T2 detection was found over long delays. The results provide further support for a cerebellar contribution to an integrated neural network recruited during temporally demanding attention-based tasks.

Impaired and preserved aspects of independent finger control in patients with cerebellar damage

The influence of the cerebellum on independent finger control has rarely been investigated. We examined multidigit control in 22 patients with cerebellar degeneration, 20 patients with cerebellar stroke, and 21 patients with surgical lesions after cerebellar tumor removal. In the first task, either the index finger or the middle finger was actively lifted from an object during static holding. Both controls and cerebellar patients increased the forces of the nearby digits in synchrony with lift-off to maintain the total finger force. Patients used increased finger forces but showed no significant deficits in the pattern and timing of rearrangement of finger forces. In the second task, subjects had to press and release one finger against a force-sensitive keypad with the other fingers being inactive. All patient groups showed increased force production of the noninstructed (enslaved) fingers compared with controls. Lesion-symptom mapping in the focal patients revealed that lesions of the superior hand area were related to abnormal levels of enslaving. Increased finger forces in the finger-lifting task likely reflect an unspecific safety strategy. Increased effects of enslaving in the individuated key-press task, however, may be explained by a deterioration of cerebellar contribution to feedforward commands necessary to suppress activity in noninstructed fingers or by increased spread of the motor command intended for the instructed finger. Despite the large and diverse patient sample, surprisingly few abnormalities were observed. Both holding an object and finger typing are overlearned, automatized motor tasks, which may not or little depend on the integrity of the cerebellum.

Cerebellar contribution to cognitive, emotional, and behavioural functions in children with cerebellar abnormalities

Cerebellar contribution to cognitive, emotional, and behavioural functions in children with cerebellar abnormalities

The cerebellar cognitive profile

The cerebellar role in non-motor functions is supported by the clinical finding that lesions confined to cerebellum produce the cerebellar cognitive affective syndrome. Nevertheless, there is no consensus regarding the overall cerebellar contribution to cognition. Among other reasons, this deficiency might be attributed to the small sample sizes and narrow breadths of existing studies on lesions in cerebellar patients, which have focused primarily on a single cognitive domain. The aim of this study was to examine the expression of cerebellar cognitive affective syndrome with regard to lesion topography in a large group of subjects with cerebellar damage. We retrospectively analysed charts from patients in the Ataxia Lab of Santa Lucia Foundation between 1997 and 2007. Of 223 charts, 156 were included in the study, focusing on the importance of the cerebellum in cognition and the relevance of lesion topography in defining the cognitive domains that have been affected. Vascular topography and the involvement of deep cerebellar nuclei were the chief factors that determined the cognitive profile. Of the various cognitive domains, the ability to sequence was the most adversely affected in nearly all subjects, supporting the hypothesis that sequencing is a basic cerebellar operation.

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.

Transcranial magnetic stimulation and motor plasticity in human lateral cerebellum: dual effect on saccadic adaptation.

The cerebellum is a key area for movement control and sensory-motor plasticity. Its medial part is considered as the exclusive cerebellar center controlling the accuracy and adaptive calibration of saccadic eye movements. However, the contribution of other zones situated in its lateral part is unknown. We addressed this question in healthy adult volunteers by using magnetic resonance imaging (MRI)-guided transcranial magnetic stimulation (TMS). The double-step target paradigm was used to adaptively lengthen or shorten saccades. TMS pulses over the right hemisphere of the cerebellum were delivered at 0, 30, or 60 ms after saccade detection in separate recording sessions. The effects on saccadic adaptation were assessed relative to a fourth session where TMS was applied to Vertex as a control site. First, TMS applied upon saccade detection before the adaptation phase reduced saccade accuracy. Second, TMS applied during the adaptation phase had a dual effect on saccadic plasticity: adaptation after-effects revealed a potentiation of the adaptive lengthening and a depression of the adaptive shortening of saccades. For the first time, we demonstrate that TMS on lateral cerebellum can influence plasticity mechanisms underlying motor performance. These findings also provide the first evidence that the human cerebellar hemispheres are involved in the control of saccade accuracy and in saccadic adaptation, with possibly different neuronal populations concerned in adaptive lengthening and shortening. Overall, these results require a reappraisal of current models of cerebellar contribution to oculomotor plasticity.

Motor deficits in neurofibromatosis type 1 mice: the role of the cerebellum

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited disease, characterized by various neurocutaneous symptoms, cognitive impairments and problems in fine and gross motor performance. Although cognitive deficits in NF1 have been attributed to increased release of the inhibitory neurotransmitter γ-amino butyric acid (GABA) in the hippocampus, the origin of the motor deficits is unknown. Cerebellar Purkinje cells, the sole output neurons of the cerebellar cortex, are GABAergic neurons and express neurofibromin at high levels, suggesting an important role for the cerebellum in the observed motor deficits in NF1. To test this, we determined the cerebellar contribution to motor problems in Nf1(+/-) mice, a validated mouse model for NF1. Using the Rotarod, a non-specific motor performance test, we confirmed that, like NF1 patients, Nf1(+/-) mice have motor deficits. Next, to evaluate the role of the cerebellum in these deficits, mice were subjected to cerebellum-specific motor performance and learning tests. Nf1(+/-) mice showed no impairment on the Erasmus ladder, as step time and number of missteps were not different. Furthermore, when compensatory eye movements were tested, no performance deficits were found in the optokinetic reflex and vestibulo-ocular reflex in the dark (VOR) or in the light (VVOR). Finally, Nf1(+/-) mice successfully completed short- and long-term VOR adaptation paradigms, tests that both depend on cerebellar function. Thus, despite the confirmed presence of motor performance problems in Nf1(+/-) mice, we found no indication of a cerebellar component. These results, combined with recent clinical data, suggest that cerebellar function is not overtly affected in NF1 patients.

2. Cerebellar contributions to cognition

2. Cerebellar contributions to cognition

The Cerebellum and Basal Ganglia are Interconnected

The cerebellum and the basal ganglia are major subcortical nuclei that control multiple aspects of behavior largely through their interactions with the cerebral cortex. Discrete multisynaptic loops connect both the cerebellum and the basal ganglia with multiple areas of the cerebral cortex. Interactions between these loops have traditionally been thought to occur mainly at the level of the cerebral cortex. Here, we review a series of recent anatomical studies in nonhuman primates that challenge this perspective. We show that the anatomical substrate exists for substantial interactions between the cerebellum and the basal ganglia. Furthermore, we discuss how these pathways may provide a useful framework for understanding cerebellar contributions to the manifestation of two prototypical basal ganglia disorders, Parkinson's disease and dystonia.

Solving the Mystery of the Human Cerebellum

The mystery of the human cerebellum is this: Why did it enlarge so dramatically in the last million years of human evolution, concomitantly with the greater enlargement of the cerebral cortex? A solution to this mystery was proposed in the 20th century as a result of research by several groups of scientists who investigated the contributions of the cerebellum to the cerebral cortex. In contrast to the 19th century investigations, which were focused on the motor functions of the cerebellum, the focus of the subsequent investigations was expanded to include some mental functions because evidence was produced that the cerebellum contributes to cognition. It was proposed that the combination in the cerebellum of motor and mental capabilities enables the cerebellum to confer on humans some adaptive advantages of great value, and this ability would explain why the human cerebellum has continued to enlarge so dramatically. A valuable adaptive advantage that is included in the proposal is the possibility that the cerebellum couples the motor function of articulating speech to the mental function that selects the language to be spoken, thus helping to produce fluent human speech and language. The validity of this proposal about linguistic processing has not yet been verified. Therefore the mystery of cerebellar enlargement in humans is not yet solved and requires further research.

Cognitive Impairment in ARCA-1, a Newly Discovered Pure Cerebellar Ataxia Syndrome

Cerebellar contribution to non-motor functions has been supported by several animal, human and functional neuroimaging studies. Which cognitive skills and to what extent the cerebrocerebellar loops contribute remain unclear, however. Among other reasons, this may be explained by the fact that authors have studied patients with extracerebellar lesions. The goal of this study was to explore the role of the cerebellum in cognition and affect in patients with autosomal recessive cerebellar ataxia type 1 (ARCA-1), a newly described inherited cerebellar disease characterised by middle-age onset of ataxia as well as pure, severe and diffuse cerebellar atrophy. To this end, the performance of 21 ARCA-1 patients was compared to that of 21 normal controls paired for age and education on a 3-h battery of attention, executive, visuospatial and memory skills. Results indicated similar IQ, naming and declarative memory abilities between groups. ARCA-1 patients showed significant deficits in attention (attention span, speed of information processing, sustained attention), verbal working memory and visuospatial/visuoconstructional skills (3-D drawings, copy of a complex figure). Functional brain imaging in a subset of patients showed diffuse severe cerebellar hypometabolism associated with a small area of right parietal hypometabolism. None of the patients presented a significant affective syndrome. Correlational analyses suggested that cognitive deficits could not be explained by the severity of motor deficits, duration of disease or mood. Altogether, this study confirms that pure cerebellar damage as seen in ARCA-1 is associated with significant cognitive impairments but not with psychiatric comorbidity. These deficits are correlated with an overall moderate impact on patient's autonomy. Our data favour an indirect participation of the dorsolateral prefrontal and posterior parietal cortical areas to the cerebrocerebellar circuit.

Reactive grip force control in persons with cerebellar stroke: effects on ipsilateral and contralateral hand

This study investigates the cerebellar contribution to reactive grip control by examining differences between (22-48 years) subjects with focal cerebellar lesion due to ischaemic stroke (CL) and healthy subjects (HS). The subjects used a pinch grip to grasp and restrain an instrumented handle from moving when it was subject to unpredictable load forces of different rates (2, 4, 8, 32 N/s) or amplitudes (1, 2, 4 N). The hand ipsilateral to the lesion of the cerebellar subjects showed delayed and more variable response latencies, e.g., 278 +/- 162 ms for loads delivered at 2 N/s, compared to HS 180 +/- 53 ms (P = 0.005). The CL also used a higher pre-load grip force with the ipsilateral hand, 1.6 +/- 0.8 N, than the HS, 1.3 +/- 0.6 N (P = 0.017). In addition, the contralateral hand in subjects with unilateral cerebellar stroke showed a delayed onset of the grip response compared to HS. Cerebellar lesions thus impair the reactive grip control both in the ipsilateral and contralateral hand.

Size of Error Affects Cerebellar Contributions to Motor Learning

Small errors may affect the process of learning in a fundamentally different way than large errors. For example, adapting reaching movements in response to a small perturbation produces generalization patterns that are different from large perturbations. Are distinct neural mechanisms engaged in response to large versus small errors? Here, we examined the motor learning process in patients with severe degeneration of the cerebellum. Consistent with earlier reports, we found that the patients were profoundly impaired in adapting their motor commands during reaching movements in response to large, sudden perturbations. However, when the same magnitude perturbation was imposed gradually over many trials, the patients showed marked improvements, uncovering a latent ability to learn from errors. On sudden removal of the perturbation, the patients exhibited aftereffects that persisted much longer than did those in healthy controls. That is, despite cerebellar damage, the brain maintained the ability to learn from small errors and the motor memory that resulted from this learning was strongly resistant to change. Of note was the fact that on completion of learning, the motor output of the cerebellar patients remained distinct from healthy controls in terms of its temporal characteristics. Therefore cerebellar degeneration impaired the ability to learn from large-magnitude errors, but had a lesser impact on learning from small errors. The neural basis of motor learning in response to small and large errors appears to be distinct.

Cerebellar Cortex Contributions to the Expression and Timing of Conditioned Eyelid Responses

We used micro-infusions during eyelid conditioning in rabbits to investigate the relative contributions of cerebellar cortex and the underlying deep nuclei (DCN) to the expression of cerebellar learning. These tests were conducted using two forms of cerebellum-dependent eyelid conditioning for which the relative roles of cerebellar cortex and DCN are controversial: delay conditioning, which is largely unaffected by forebrain lesions, and trace conditioning, which involves interactions between forebrain and cerebellum. For rabbits trained with delay conditioning, silencing cerebellar cortex by micro-infusions of the local anesthetic lidocaine unmasked stereotyped short-latency responses. This was also the case after extinction as observed previously with reversible blockade of cerebellar cortex output. Conversely, increasing cerebellar cortex activity by micro-infusions of the GABA(A) antagonist picrotoxin reversibly abolished conditioned responses. Effective cannula placements were clustered around the primary fissure and deeper in lobules hemispheric lobule IV (HIV) and hemispheric lobule V (HV) of anterior lobe. In well-trained trace conditioned rabbits, silencing this same area of cerebellar cortex or reversibly blocking cerebellar cortex output also unmasked short-latency responses. Because Purkinje cells are the sole output of cerebellar cortex, these results provide evidence that the expression of well-timed conditioned responses requires a well-timed decrease in the activity of Purkinje cells in anterior lobe. The parallels between results from delay and trace conditioning suggest similar contributions of plasticity in cerebellar cortex and DCN in both instances.