scholarly journals Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex

2021 ◽  
Author(s):  
Chong Guo ◽  
Stephanie Rudolph ◽  
Morgan E. Neuwirth ◽  
Wade G. Regehr
Keyword(s):  
Purkinje Cell ◽  
Cerebellar Cortex ◽  
Mossy Fiber ◽  
Input Output ◽  
Brush Cells ◽  
Unipolar Brush Cells ◽  
Input Layer ◽  
Inhibitory Feedback ◽  
Almost All ◽  
Control Balance

AbstractCircuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), and Purkinje cell (PC) synapses made by axon collaterals in the granular layer, are both enriched in areas that control balance and eye-movement. Here we find a link between these specializations: PCs preferentially inhibit mGluR1-expressing UBCs that respond to mossy fiber inputs with long lasting increases in firing, but PCs do not inhibit mGluR1-lacking UBCs. PCs inhibit about 29% of mGluR1-expressing UBCs by activating GABAA receptors (GABAARs) and inhibit almost all mGluR1-expressing UBCs by activating GABABRs. PC to UBC synapses allow PC output to regulate the input layer of the cerebellar cortex in diverse ways. GABAAR-mediated feedback is fast, unreliable, noisy, and suited to linearizing input-output curves and decreasing gain. Slow GABABR-mediated inhibition allows elevated PC activity to sharpen the input-output transformation of UBCs, and allows dynamic inhibitory feedback of mGluR1-expressing UBCs.

scholarly journals Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Chong Guo ◽  
Stephanie Rudolph ◽  
Morgan E Neuwirth ◽  
Wade G Regehr
Keyword(s):  
Purkinje Cell ◽  
Cerebellar Cortex ◽  
Metabotropic Glutamate Receptor ◽  
Mossy Fiber ◽  
Brush Cells ◽  
Metabotropic Glutamate ◽  
Unipolar Brush Cells ◽  
Input Layer ◽  
Almost All ◽  
Control Balance

Circuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), and Purkinje cell (PC) synapses made by axon collaterals in the granular layer, are both enriched in areas that control balance and eye movement. Here, we find a link between these specializations in mice: PCs preferentially inhibit metabotropic glutamate receptor type 1 (mGluR1)-expressing UBCs that respond to mossy fiber (MF) inputs with long lasting increases in firing, but PCs do not inhibit mGluR1-lacking UBCs. PCs inhibit about 29% of mGluR1-expressing UBCs by activating GABAA receptors (GABAARs) and inhibit almost all mGluR1-expressing UBCs by activating GABAB receptors (GABABRs). PC to UBC synapses allow PC output to regulate the input layer of the cerebellar cortex in diverse ways. Based on optogenetic studies and a small number of paired recordings, GABAAR-mediated feedback is fast and unreliable. GABABR-mediated inhibition is slower and is sufficiently large to strongly influence the input-output transformations of mGluR1-expressing UBCs.

scholarly journals Early Onset of Ataxia in Moonwalker Mice Is Accompanied by Complete Ablation of Type II Unipolar Brush Cells and Purkinje Cell Dysfunction

2013 ◽  
Vol 33 (50) ◽  
pp. 19689-19694 ◽  
Author(s):  
G. Sekerkova ◽  
J.-A. Kim ◽  
M. J. Nigro ◽  
E. B. E. Becker ◽  
J. Hartmann ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Early Onset ◽  
Type Ii ◽  
Brush Cells ◽  
Cell Dysfunction ◽  
Complete Ablation ◽  
Unipolar Brush Cells

scholarly journals Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse

2020 ◽  
Author(s):  
Timothy S. Balmer ◽  
Carolina Borges-Merjane ◽  
Laurence O. Trussell
Keyword(s):  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Synaptic Cleft ◽  
Synaptic Activity ◽  
Brush Cells ◽  
Incomplete Removal ◽  
Unipolar Brush Cells ◽  
Ambient Glutamate ◽  
Synaptic Responses

AbstractSynapses of glutamatergic mossy fiber onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBC. The source of ambient glutamate was spontaneous, spike-independent exocytosis from the mossy fiber terminal, and its level was dependent on activity of glutamate transporters EAAT1-2. Changing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.

scholarly journals Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Timothy S Balmer ◽  
Carolina Borges-Merjane ◽  
Laurence O Trussell
Keyword(s):  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Synaptic Cleft ◽  
Synaptic Activity ◽  
Brush Cells ◽  
Incomplete Removal ◽  
Unipolar Brush Cells ◽  
Ambient Glutamate

Synapses of glutamatergic mossy fibers onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC's large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the mossy fiber terminal, and its level was dependent on activity of glutamate transporters EAAT1-2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.

Purkinje cell phenotype restricts the distribution of unipolar brush cells

Neuroscience ◽  
2009 ◽  
Vol 164 (4) ◽  
pp. 1496-1508 ◽  
Author(s):  
S.-H. Chung ◽  
R.V. Sillitoe ◽  
L. Croci ◽  
A. Badaloni ◽  
G. Consalez ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Cell Phenotype ◽  
Brush Cells ◽  
Unipolar Brush Cells

scholarly journals Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chong Guo ◽  
Vincent Huson ◽  
Evan Z. Macosko ◽  
Wade G. Regehr
Keyword(s):  
Mossy Fiber ◽  
Temporal Integration ◽  
Response Duration ◽  
Molecular Properties ◽  
Multiple Time Scales ◽  
Multiple Time ◽  
Brush Cells ◽  
Unipolar Brush Cells ◽  
Response Profiles ◽  
Metabotropic Signaling

AbstractMany neuron types consist of populations with continuously varying molecular properties. Here, we show a continuum of postsynaptic molecular properties in three types of neurons and assess the functional correlates in cerebellar unipolar brush cells (UBCs). While UBCs are generally thought to form discrete functional subtypes, with mossy fiber (MF) activation increasing firing in ON-UBCs and suppressing firing in OFF-UBCs, recent work also points to a heterogeneity of response profiles. Indeed, we find a continuum of response profiles that reflect the graded and inversely correlated expression of excitatory mGluR1 and inhibitory mGluR2/3 pathways. MFs coactivate mGluR2/3 and mGluR1 in many UBCs, leading to sequential inhibition-excitation because mGluR2/3-currents are faster. Additionally, we show that DAG-kinase controls mGluR1 response duration, and that graded DAG kinase levels correlate with systematic variation of response duration over two orders of magnitude. These results demonstrate that continuous variations in metabotropic signaling can generate a stable cell-autonomous basis for temporal integration and learning over multiple time scales.

scholarly journals Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Timothy S Balmer ◽  
Laurence O Trussell
Keyword(s):  
Granule Cells ◽  
Mossy Fiber ◽  
Vestibular Nucleus ◽  
Mossy Fibers ◽  
Primary Afferents ◽  
Vestibular Organ ◽  
Brush Cells ◽  
Unipolar Brush Cell ◽  
Selective Targeting ◽  
Unipolar Brush Cells

In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes in mice. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.

Sign in / Sign up

Export Citation Format

Share Document