Cerebellar cortex

2020 ◽  
pp. 497-504
Author(s):  
Edmund T. Rolls
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Network Architecture ◽  
Granule Cells ◽  
Feedforward Control ◽  
Synaptic Depression ◽  
Climbing Fibre ◽  
Regular Sampling

The cerebellar cortex appears to be involved in predictive feedforward control to generate smooth movements. There is a beautiful network architecture which suggests that the granule cells perform expansion recoding of the inputs; that these connect to the Purkinje cells via an architecture that ensures regular sampling; and that each Purkinje cell has a single teacher, the climbing fibre, which produces associative long-term synaptic depression as part of perceptron-like learning.

scholarly journals Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ryan T Willett ◽  
N Sumru Bayin ◽  
Andrew S Lee ◽  
Anjana Krishnamurthy ◽  
Alexandre Wojcinski ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Granule Cells ◽  
Postnatal Growth ◽  
Cerebellar Nuclei ◽  
Cell Number ◽  
Conditional Knockout ◽  
Neural Systems ◽  
Scaling Down

For neural systems to function effectively, the numbers of each cell type must be proportioned properly during development. We found that conditional knockout of the mouse homeobox genes En1 and En2 in the excitatory cerebellar nuclei neurons (eCN) leads to reduced postnatal growth of the cerebellar cortex. A subset of medial and intermediate eCN are lost in the mutants, with an associated cell non-autonomous loss of their presynaptic partner Purkinje cells by birth leading to proportional scaling down of neuron production in the postnatal cerebellar cortex. Genetic killing of embryonic eCN throughout the cerebellum also leads to loss of Purkinje cells and reduced postnatal growth but throughout the cerebellar cortex. Thus, the eCN play a key role in scaling the size of the cerebellum by influencing the survival of their Purkinje cell partners, which in turn regulate production of granule cells and interneurons via the amount of sonic hedgehog secreted.

scholarly journals Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons

Neuron ◽  
2016 ◽  
Vol 91 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Laurens Witter ◽  
Stephanie Rudolph ◽  
R. Todd Pressler ◽  
Safiya I. Lahlaf ◽  
Wade G. Regehr
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cerebellar Cortex

scholarly journals Purkinje Cells Directly Inhibit Granule Cells in Specialized Regions of the Cerebellar Cortex

Neuron ◽  
2016 ◽  
Vol 91 (6) ◽  
pp. 1330-1341 ◽  
Author(s):  
Chong Guo ◽  
Laurens Witter ◽  
Stephanie Rudolph ◽  
Hunter L. Elliott ◽  
Katelin A. Ennis ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Granule Cells

scholarly journals Purkinje cell intrinsic excitability increases after synaptic long term depression

2016 ◽  
Vol 116 (3) ◽  
pp. 1208-1217 ◽  
Author(s):  
Zhen Yang ◽  
Fidel Santamaria
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Input Resistance ◽  
Parallel Fiber ◽  
Intrinsic Excitability ◽  
Hcn Channel ◽  
Membrane Excitability ◽  
Fiber System ◽  
Long Term Depression

Coding in cerebellar Purkinje cells not only depends on synaptic plasticity but also on their intrinsic membrane excitability. We performed whole cell patch-clamp recordings of Purkinje cells in sagittal cerebellar slices in mice. We found that inducing long-term depression (LTD) in the parallel fiber to Purkinje cell synapses results in an increase in the gain of the firing rate response. This increase in excitability is accompanied by an increase in the input resistance and a decrease in the amplitude of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated voltage sag. Application of a HCN channel blocker prevents the increase in input resistance and excitability without blocking the expression of synaptic LTD. We conclude that the induction of parallel fiber-Purkinje cell LTD is accompanied by an increase in excitability of Purkinje cells through downregulation of the HCN-mediated h current. We suggest that HCN downregulation is linked to the biochemical pathway that sustains synaptic LTD. Given the diversity of information carried by the parallel fiber system, we suggest that changes in intrinsic excitability enhance the coding capacity of the Purkinje cell to specific input sources.

scholarly journals Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss

2008 ◽  
Vol 295 (2) ◽  
pp. R596-R603 ◽  
Author(s):  
Jayanth Ramadoss ◽  
Emilie R. Lunde ◽  
Nengtai Ouyang ◽  
Wei-Jung A. Chen ◽  
Timothy A. Cudd
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Granule Cells ◽  
Cell Number ◽  
Ethanol Exposure ◽  
Ph Sensitive ◽  
Mitigation Strategies ◽  
Cerebellar Purkinje Cell ◽  
Prenatal Ethanol Exposure ◽  
Channel Inhibition

Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258 ± 10 mg/dl peak blood ethanol concentration) or saline in a “3 days/wk binge” pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

scholarly journals A Late Phase of Long-Term Synaptic Depression in Cerebellar Purkinje Cells Requires Activation of MEF2

Cell Reports ◽  
2019 ◽  
Vol 26 (5) ◽  
pp. 1089-1097.e3 ◽  
Author(s):  
Milena M. Andzelm ◽  
Devorah Vanness ◽  
Michael E. Greenberg ◽  
David J. Linden
Keyword(s):  
Purkinje Cells ◽  
Late Phase ◽  
Synaptic Depression ◽  
Cerebellar Purkinje Cells

Serotonergic modulation of evoked responses in turtle cerebellar Purkinje cells

1996 ◽  
Vol 76 (5) ◽  
pp. 3102-3113 ◽  
Author(s):  
H. Lu ◽  
L. J. Larson-Prior
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cell Layer ◽  
Response Amplitude ◽  
Evoked Responses ◽  
Postsynaptic Potentials ◽  
Control Value ◽  
Bath Application ◽  
Cerebellar Peduncle

1. Immunocytochemical studies of the turtle brain revealed the presence of serotonin (5-hydroxytryptamine, 5-HT) immunoreactive (5-HT-ir) processes in the granule and Purkinje cell layers, but not in the molecular layer (ML), of the cerebellar cortex. Immunoreactive axonal profiles were present throughout the granule cell layer (GCL) where they generally coursed in an anteroposterior direction and could frequently be seen to ascend toward the Purkinje cell layer (PCL). Occasional 5-HT-ir processes were observed adjacent to Purkinje cell somata. 2. The effects of exogenously applied serotonin on mossy fiber and parallel fiber evoked responses in turtle Purkinje cells were examined by use of intrasomatic and intradendritic recordings in an intact cerebellar preparation in vitro. 3. Bath application of serotonin (0.2–1.0 microM) produced a dose-dependent reduction in Purkinje cell membrane resistance, which was not correlated with changes in postsynaptic response amplitude. At 5-HT concentrations > 1.0 microM (0.01–5 mM), resistance values returned to control levels. No consistent changes in spike width or postspike afterhyperpolarization were seen in response to serotonin application, nor were endogenous pacemaker-like discharges affected. Firing rate, assessed as threshold response to depolarizing current injection (0.3–1.0 nA, 1 s duration), was increased in 51% and decreased in 40% of cells tested. 4. Single stimuli delivered to either the cerebellar peduncle or the GCL resulted in the activation of fast excitatory postsynaptic potentials (fEPSP). These responses were dose dependently reduced in amplitude by bath application of serotonin (0.2–1.0 microM). At concentrations ranging from 10 to 100 microM, the response amplitude following agonist application plateaued at approximately 70% of control value. With higher dose applications (0.5-5 mM) of serotonin, the response amplitude exhibited a steep reduction (from 65-10% of control value). 5. Brief trains of stimuli (5 stimuli, 50 Hz) delivered to either the cerebellar peduncle or the GCL resulted in the activation of slow excitatory postsynaptic potentials (sEPSP). The peak amplitude of this response was unaffected by bath application of serotonin at concentrations ranging from 0.2 to 100 microM. At higher concentrations (0.5–5 mM), the sEPSP peak amplitude was dose-dependently reduced, with the largest amplitude reduction seen after peduncular stimulation. 6. It is suggested that serotonin acts as a modulator of fast excitatory synaptic activity in the cerebellar cortex, while exerting little affect on slow excitatory events. The fact that serotonin preferentially affects fast excitatory transmission may have important implications for the integration of incoming sensory signals at both the granule and Purkinje cell level.

scholarly journals Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

2008 ◽  
Vol 100 (6) ◽  
pp. 3167-3174 ◽  
Author(s):  
Amor Belmeguenai ◽  
Paolo Botta ◽  
John T. Weber ◽  
Mario Carta ◽  
Martijn De Ruiter ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Motor Learning ◽  
Synaptic Transmission ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Parallel Fiber ◽  
Calcium Currents ◽  
Long Term Depression

Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF–LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)–dependent responses in Purkinje cells, both of which are involved in PF–LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF–LTP and that PF–LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF–LTD could contribute to the motor coordination deficits resulting from alcohol consumption.

Dynamic Synchronization of Purkinje Cell Simple Spikes

2006 ◽  
Vol 96 (6) ◽  
pp. 3485-3491 ◽  
Author(s):  
Soon-Lim Shin ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Firing Rate ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cerebellar Nuclei ◽  
Temporal Coding ◽  
Sharp Peak ◽  
Deep Cerebellar Nuclei

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

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