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

Connor, Steve; Bloomfield, J.; LeBoutillier, Janelle C.; Thompson, Richard F.; Petit, Ted L.; Weeks, Andrew C.W.

doi:10.1037/a0016370

Cited by 15 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous in vitro studies have shown decreases in synaptic AMPAR responses in slice preparations but no structural changes after LTD induction in cultured PCs (24). Other in vivo studies demonstrated PF-PC synaptogenesis induced by learning a complex acrobatic motor skill (25) or PF-PC elimination by eyeblink conditioning (26). In the vestibular ocular reflex (VOR), which shares common output pathways with HOKR (1, 4), gaindecrease but not gain-increase adaptation was improved by estradiol treatment, which also increased PF-PC synapse density (27).…”

Section: Discussionmentioning

confidence: 97%

Distinct cerebellar engrams in short-term and long-term motor learning

Wang

Nakadate

Masugi-Tokita

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-term adaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short-and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.long-term depression | high-voltage electron microscope | Golgi staining I mage stabilization in the visual field via the vestibulo-ocular reflex and optokinetic response requires accurate extraocular muscle synergies that rely on long-term plastic calibrations in the cerebellar flocculus (FL) and its downstream target vestibular nuclei (VN) (1-8). Long-term depression (LTD) in parallel fiber-Purkinje cell (PF-PC) synapses has been postulated as a possible mechanism for this plastic calibration based on many lines of mutant mice that lack both LTD and learning (9-12). However, LTD's role in motor learning has been recently questioned by a few mutant mice lines (13) and mice with pharmacological treatments (14) that showed lack of LTD but no impairment of learning. Furthermore, long-term potentiation in PF-PC synapses has been also shown to be involved in the motor learning (15). Recent evidence indicates that various forms of synaptic plasticity works synergistically and can compensate each other when one is missing in cerebellar motor learning (16). Despite the apparently contradictory results, no direct evidence for the decrease or increase of synaptic AMPA receptors (AMPARs) has been shown in physiological motor learning. To elucidate in vivo neuronal substrates for motor learning in wildtype mouse, we examined individual PF-PC synapses using quantitative SDS-digested freeze-fracture replica labeling (SDS-FRL) (17) combined with morphometric EM analysis after adaptation of ho...

show abstract

Section: Discussionmentioning

confidence: 97%

Distinct cerebellar engrams in short-term and long-term motor learning

Wang

Nakadate

Masugi-Tokita

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The other possibility is that the protein synthesis may be related to restructuring of cerebellar cortical neural circuitry. A decrease in the number of pf-PC synapses has been suggested in the rabbit cerebellar hemisphere after acquisition of eyeblink conditioning (Connor et al, 2009) and in the mouse flocculus after long-term HOKR adaptation (Nakadate et al, 2004). The reduced pf-PC synapses may decrease the tonic inhibitory drive of Purkinje cells on vestibular or cerebellar nuclear neurons.…”

Section: Role Of Protein Synthesis In Memory Transfermentioning

confidence: 98%

Role of Cerebellar Cortical Protein Synthesis in Transfer of Memory Trace of Cerebellum-Dependent Motor Learning

Okamoto¹,

Endo²,

Shirao³

et al. 2011

Journal of Neuroscience

View full text Add to dashboard Cite

“…Changes in synapse structure have also been found in the cerebellar cortex following eyeblink conditioning. Rabbits given 3 d of eyeblink conditioning showed a reduction of excitatory parallel fiber synapses with Purkinje cells (Connor et al 2009). Thus, the morphological studies of synaptic plasticity have found synaptic changes that might underlie an LTP-like mechanism in the anterior interpositus nucleus and an LTD-like mechanism in the cerebellar cortex.…”

Section: Localization Of the Memory Trace Within The Cerebellummentioning

confidence: 99%

Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

Freeman¹,

Steinmetz²

2011

Learn. Mem.

176

162

View full text Add to dashboard Cite

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.Eyeblink conditioning is an associative learning paradigm that was first developed for use in human participants in the 1920s (Cason 1922). It was initially valued as a method for studying learning and higher nervous system function without confounds associated with verbal reports, introspection, or prior experience with similar associations. The procedure involves presentation of a conditioned stimulus (CS), typically a tone or light, which is paired with an unconditioned stimulus (US) that reliably elicits eyelid closure, such as an air puff or brief electrical stimulation near the eye. Humans will often show a short-latency lowamplitude unconditioned (alpha) response to an auditory CS. After repeated CS-US trials, conditioned eyelid closure (conditioned response [CR]) occurs during the CS. Maximum eyelid closure for the CR typically occurs near the onset time of the US. Several shortcomings of the paradigm were later identified, most notably, the presence of alpha responses and voluntary responses among human participants who became explicitly aware of the stimulus contingency. These shortcomings and the need for an animal model for invasive neuroscience research led to the development of the rabbit eyeblink and nictitating membrane paradigms Schneiderman et al. 1962;Gormezano 1966). Rabbits tolerate restraint well, do not exhibit alpha responses, and precise measures of eyelid closure and nictitating membrane movement are obtained readily (Gormezano 1966). Most of the initial work on the neural mechanisms underlying eyeblink conditioning was conducted using rabbits, but the paradigm has been applied to frogs, turtles, mice, rats, ferrets, sheep, dogs, monkeys, and cats. A concern with using species other...

show abstract

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

Cited by 15 publications

References 37 publications

Distinct cerebellar engrams in short-term and long-term motor learning

Distinct cerebellar engrams in short-term and long-term motor learning

Role of Cerebellar Cortical Protein Synthesis in Transfer of Memory Trace of Cerebellum-Dependent Motor Learning

Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

Contact Info

Product

Resources

About