scholarly journals Intrinsic Excitability Increase in Cerebellar Purkinje Cells Following Delay Eyeblink Conditioning in Mice

2018 ◽  
Author(s):  
Heather K. Titley ◽  
Gabrielle V. Watkins ◽  
Carmen Lin ◽  
Craig Weiss ◽  
Michael McCarthy ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Neuronal Excitability ◽  
Eyeblink Conditioning ◽  
Underlying Mechanism ◽  
Learning Task ◽  
Sk Channels ◽  
Calcium Dependent ◽  
Cerebellar Learning ◽  
Intrinsic Plasticity ◽  
Cerebellar Purkinje Cells

AbstractCerebellar learning is canonically thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the down-regulation of calcium-dependent SK-type K channels, which is associated with an increase in neuronal excitability. In the hippocampus, SK-mediated intrinsic plasticity has been shown to play a role in trace eyeblink conditioning; however, it is not yet known how intrinsic plasticity contributes to a cerebellar learning task such as delay eyeblink conditioning. Whole cell recordings were obtained from acute cerebellar slices from mice ~48 hours after learning a delay eyeblink conditioning task. Over a period of repeated training sessions mice received either distinctly paired trials of a tone co-terminating with a periorbital shock (conditioned mice) or trials in which these stimuli were presented in an unpaired manner (pseudoconditioned mice). Conditioned mice show a significantly reduced afterhyperpolarization (AHP) following trains of parallel fiber stimuli. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eyeblink conditioning and point toward a downregulation of SK channels as a potential underlying mechanism.

scholarly journals mGlu1 receptor mediates homeostatic control of intrinsic excitability through Ih in cerebellar Purkinje cells

2016 ◽  
Vol 115 (5) ◽  
pp. 2446-2455 ◽  
Author(s):  
Hyun Geun Shim ◽  
Sung-Soo Jang ◽  
Dong Cheol Jang ◽  
Yunju Jin ◽  
Wonseok Chang ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Neuronal Activity ◽  
Metabotropic Glutamate Receptor ◽  
Activity Level ◽  
Network Activity ◽  
Firing Rates ◽  
Metabotropic Glutamate ◽  
Gated Channel ◽  
Intrinsic Plasticity ◽  
Cerebellar Purkinje Cells

Homeostatic intrinsic plasticity is a cellular mechanism for maintaining a stable neuronal activity level in response to developmental or activity-dependent changes. Type 1 metabotropic glutamate receptor (mGlu1 receptor) has been widely known to monitor neuronal activity, which plays a role as a modulator of intrinsic and synaptic plasticity of neurons. Whether mGlu1 receptor contributes to the compensatory adjustment of Purkinje cells (PCs), the sole output of the cerebellar cortex, in response to chronic changes in excitability remains unclear. Here, we demonstrate that the mGlu1 receptor is involved in homeostatic intrinsic plasticity through the upregulation of the hyperpolarization-activated current ( Ih) in cerebellar PCs. This plasticity was prevented by inhibiting the mGlu1 receptor with Bay 36–7620, an mGlu1 receptor inverse agonist, but not with CPCCOEt, a neutral antagonist. Chronic inactivation with tetrodotoxin (TTX) increased the components of Ih in the PCs, and ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated channel selective inhibitor, fully restored reduction of firing rates in the deprived neurons. The homeostatic elevation of Ih was also prevented by BAY 36–7620, but not CPCCOEt. Furthermore, KT 5720, a blocker of protein kinase A (PKA), prevented the effect of TTX reducing the evoked firing rates, indicating the reduction in excitability of PCs due to PKA activation. Our study shows that both the mGlu1 receptor and the PKA pathway are involved in the homeostatic intrinsic plasticity of PCs after chronic blockade of the network activity, which provides a novel understanding on how cerebellar PCs can preserve the homeostatic state under activity-deprived conditions.

scholarly journals TRPC3 is essential for functional heterogeneity of cerebellar Purkinje cells

2018 ◽  
Author(s):  
Bin Wu ◽  
Francois G.C. Blot ◽  
Aaron B. Wong ◽  
Catarina Osório ◽  
Youri Adolfs ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Transient Receptor Potential ◽  
Eyeblink Conditioning ◽  
Receptor Potential ◽  
Cellular Heterogeneity ◽  
Loss Of Function ◽  
Functional Heterogeneity ◽  
Homogeneous Population ◽  
Cerebellar Purkinje Cells

AbstractDespite the canonical homogenous character of its organization, the cerebellum plays differential computational roles in distinct types of sensorimotor behaviors. However, the molecular and cell physiological underpinnings are unclear. Here we determined the contribution of transient receptor potential cation channel type C3 (TRPC3) to signal processing in different cerebellar modules. Using gain-of-function and loss-of-function mouse models, we found that TRPC3 controls the simple spike activity of zebrin-negative (Z–), but not of zebrin-positive (Z+), Purkinje cells. Moreover, in vivo TRPC3 also regulated complex spike firing and its interaction with simple spikes exclusively in Z– Purkinje cells. Finally, we found that eyeblink conditioning, related to Z– modules, but not compensatory eye movement adaptation, linked to Z+ modules, was affected in TRPC3 loss-of-function mice. Together, our results indicate that TRPC3 is essential for the cellular heterogeneity that introduces distinct physiological properties in an otherwise homogeneous population of Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration.

Learning-Induced Reversal of the Effect of Noradrenalin on the Postburst AHP

2006 ◽  
Vol 96 (4) ◽  
pp. 1728-1733 ◽  
Author(s):  
Inbar Brosh ◽  
Kobi Rosenblum ◽  
Edi Barkai
Keyword(s):  
Potassium Current ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Sk Channels ◽  
Similar Extent ◽  
Protein Expression Level ◽  
Calcium Dependent ◽  
The Difference ◽  
Small Conductance

Pyramidal neurons in the piriform cortex from olfactory-discrimination–trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, IAHP and s IAHP, that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks IAHP, reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance IAHP while suppressing S IAHP, reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the IAHP current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, s IAHP. Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.

Effect of Conditioned Stimulus Parameters on Timing of Conditioned Purkinje Cell Responses

2010 ◽  
Vol 103 (3) ◽  
pp. 1329-1336 ◽  
Author(s):  
Pär Svensson ◽  
Dan-Anders Jirenhed ◽  
Fredrik Bengtsson ◽  
Germund Hesslow
Keyword(s):  
Conditioned Stimulus ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Mossy Fiber ◽  
Eyeblink Conditioning ◽  
Mossy Fibers ◽  
Inhibitory Response ◽  
Cell Responses ◽  
Cerebellar Purkinje Cells ◽  
Adaptive Timing

Pavlovian eyeblink conditioning is a useful experimental model for studying adaptive timing, an important aspect of skilled movements. The conditioned response (CR) is precisely timed to occur just before the onset of the expected unconditioned stimulus (US). The timing can be changed immediately, however, by varying parameters of the conditioned stimulus (CS). It has previously been shown that increasing the intensity of a peripheral CS or the frequency of a CS consisting of a train of stimuli to the mossy fibers shortens the latency of the CR. The adaptive timing of behavioral CRs probably reflects the timing of an underlying learned inhibitory response in cerebellar Purkinje cells. It is not known how the latency of this Purkinje cell CR is controlled. We have recorded form Purkinje cells in conditioned decerebrate ferrets while increasing the intensity of a peripheral CS or the frequency of a mossy fiber CS. We observe changes in the timing of the Purkinje cell CR that match the behavioral effects. The results are consistent with the effect of CS parameters on behavioral CR latency being caused by corresponding changes in Purkinje cell CRs. They suggest that synaptic temporal summation may be one of several mechanisms underlying adaptive timing of movements.

scholarly journals Learned response sequences in cerebellar Purkinje cells

2017 ◽  
Vol 114 (23) ◽  
pp. 6127-6132 ◽  
Author(s):  
Dan-Anders Jirenhed ◽  
Anders Rasmussen ◽  
Fredrik Johansson ◽  
Germund Hesslow
Keyword(s):  
Purkinje Cells ◽  
Interstimulus Interval ◽  
Response Pattern ◽  
Mossy Fiber ◽  
Eyeblink Conditioning ◽  
Complex Motor ◽  
Cerebellar Purkinje Cells ◽  
Single Response ◽  
The Right ◽  
Stimulation Of

Associative learning in the cerebellum has previously focused on single movements. In eyeblink conditioning, for instance, a subject learns to blink at the right time in response to a conditional stimulus (CS), such as a tone that is repeatedly followed by an unconditional corneal stimulus (US). During conditioning, the CS and US are transmitted by mossy/parallel fibers and climbing fibers to cerebellar Purkinje cells that acquire a precisely timed pause response that drives the overt blink response. The timing of this conditional Purkinje cell response is determined by the CS–US interval and is independent of temporal patterns in the input signal. In addition to single movements, the cerebellum is also believed to be important for learning complex motor programs that require multiple precisely timed muscle contractions, such as, for example, playing the piano. In the present work, we studied Purkinje cells in decerebrate ferrets that were conditioned using electrical stimulation of mossy fiber and climbing fiber afferents as CS and US, while alternating between short and long interstimulus intervals. We found that Purkinje cells can learn double pause responses, separated by an intermediate excitation, where each pause corresponds to one interstimulus interval. The results show that individual cells can not only learn to time a single response but that they also learn an accurately timed sequential response pattern.

The neuronal EF-hand calcium-binding protein visinin-like protein-3 is expressed in cerebellar Purkinje cells and shows a calcium-dependent membrane association

Neuroscience ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 121-129 ◽  
Author(s):  
C. Spilker ◽  
K. Richter ◽  
K.-H. Smalla ◽  
D. Manahan-Vaughan ◽  
E.D. Gundelfinger ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Calcium Binding ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Membrane Association ◽  
Calcium Dependent ◽  
Ef Hand ◽  
Cerebellar Purkinje Cells

scholarly journals Intrinsic Plasticity of Cerebellar Purkinje Cells Contributes to Motor Memory Consolidation

2020 ◽  
Vol 40 (21) ◽  
pp. 4145-4157 ◽  
Author(s):  
Dong Cheol Jang ◽  
Hyun Geun Shim ◽  
Sang Jeong Kim
Keyword(s):  
Purkinje Cells ◽  
Memory Consolidation ◽  
Motor Memory ◽  
Intrinsic Plasticity ◽  
Cerebellar Purkinje Cells

Pavlovian eyeblink conditioning is severely impaired in tottering mice

2020 ◽  
Author(s):  
Nina L. de Oude ◽  
Freek E. Hoebeek ◽  
Michiel M. ten Brinke ◽  
Chris I. de Zeeuw ◽  
Henk-Jan Boele
Keyword(s):  
Neuronal Excitability ◽  
Eyeblink Conditioning ◽  
Learning Task ◽  
Loss Of Function ◽  
Oscillatory State ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Dependent Learning ◽  
The Brain ◽  
Normal Calcium

Cacna1a encodes the pore-forming α1A subunit of CaV2.1 voltage-dependent calcium channels, which regulate neuronal excitability and synaptic transmission. Purkinje cells in the cortex of cerebellum abundantly express these CaV2.1 channels. Here, we show that homozygous tottering (tg) mice, which carry a loss-of-function Cacna1a mutation, exhibit severely impaired learning in Pavlovian eyeblink conditioning, which is a cerebellar dependent learning task. Performance of reflexive eyeblinks is unaffected in tg mice. Transient seizure activity in tg mice further corrupted the amplitude of eyeblink CRs. Our results indicate that normal calcium homeostasis is imperative for cerebellar learning and that the oscillatory state of the brain can affect the expression thereof.

scholarly journals Intrinsic plasticity of cerebellar Purkinje cells in motor learning circuits

2019 ◽  
Author(s):  
Dong Cheol Jang ◽  
Hyun Geun Shim ◽  
Sang Jeong Kim
Keyword(s):  
Purkinje Cells ◽  
Neural Plasticity ◽  
Memory Consolidation ◽  
Vestibular Nucleus ◽  
Motor Memory ◽  
Long Term Storage ◽  
Vestibulo Ocular Reflex ◽  
Intrinsic Plasticity ◽  
Cerebellar Purkinje Cells ◽  
Local Circuits

AbstractIntrinsic plasticity of cerebellar Purkinje cells (PCs) is recently highlighted in the cerebellar local circuits, however, its physiological impact on the cerebellar learning and memory remains elusive. Using a mouse model of memory consolidation deficiency, we found that the intrinsic plasticity of PCs may be involved in motor memory consolidation. Gain-up training of the vestibulo-ocular reflex produced a decrease in the synaptic weight of PCs in both the wild-type and knockout groups. However, intrinsic plasticity was impaired only in the knockout mice. Furthermore, the observed defects in the intrinsic plasticity of PCs led to the formation of improper neural plasticity in the vestibular nucleus (VN) neurons. Our results suggest that the synergistic modulation of intrinsic and synaptic plasticity in PCs is required for the changes in following plasticity in the VN, thereby contributes to the long-term storage of motor memory.

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