scholarly journals Activation of Extrasynaptic NMDARs at Individual Parallel Fiber-Molecular Layer Interneuron Synapses in Cerebellum

2013 ◽  
Vol 33 (41) ◽  
pp. 16323-16333 ◽  
Author(s):  
B. Nahir ◽  
C. E. Jahr
Keyword(s):  
Molecular Layer ◽  
Parallel Fiber ◽  
Molecular Layer Interneuron

Glutamate microinjections in cerebellar cortex reproduce cerebrovascular effects of parallel fiber stimulation

1996 ◽  
Vol 271 (6) ◽  
pp. R1568-R1575 ◽  
Author(s):  
G. Yang ◽  
C. Iadecola
Keyword(s):  
Glutamate Receptors ◽  
Cerebellar Cortex ◽  
Glutamate Release ◽  
Molecular Layer ◽  
Parallel Fiber ◽  
Synaptic Activity ◽  
No Production ◽  
Doppler Flowmetry ◽  
Cranial Window ◽  
Fiber Stimulation

Electrical stimulation of cerebellar parallel fibers releases glutamate and increases local blood flow (BFcrb), an effect in part mediated by glutamate-induced nitric oxide (NO) production. We studied whether local microinjection of glutamate into the cerebellar cortex would produce increases in BFcrb comparable to those elicited by parallel fiber stimulation. In halothane-anesthetized rats equipped with a cranial window, glutamate was microinjected into the cerebellar molecular layer, and BFcrb was monitored by laser-Doppler flowmetry. Glutamate microinjections increased BFcrb dose dependently (2-200 pmol in 200 nl) (n = 9) and by 55 +/- 6% at 200 pmol (mean +/- SE). The magnitude and temporal profile of the increases in BFcrb compared favorably with the increase in flow produced by parallel fiber stimulation. The glutamate-induced BFcrb increase was attenuated by superfusion with the Na2+ channel blocker tetrodotoxin (10 microM; -50 +/- 10%; n = 5; P < 0.05; t-test) or by blocking synaptic activity by treatment of the cerebellar cortex with Ringer containing 20 mM Mg2+ and 0 mM Ca2+ (-80 +/- 4%; n = 6; P < 0.05). The glutamate-receptor antagonist kynurenate (10 mM) attenuated the increase in BFcrb by 59 +/- 6% (P < 0.05; n = 5). The relatively selective inhibitor of neuronal NO synthase 7-nitroindazole (100 mg/kg ip) reduced the flow response evoked by microinjection of glutamate (-46 +/- 7%; n = 5; P < 0.05) but not acetylcholine (10 microM; P > 0.05; n = 6). We conclude that glutamate microinjections increase local BFcrb via activation of glutamate receptors. The glutamate-induced vasodilation is mediated, in part, by neurally derived NO. The striking similarities between the vascular responses evoked by parallel fiber stimulation and that produced by microinjection of glutamate support the hypothesis that the increase in BFcrb produced by parallel fiber stimulation is mediated by glutamate release and activation of glutamate receptors. The data also strengthen the hypothesis that glutamate and NO are important mediators in the mechanisms linking synaptic activity to BFcrb in cerebellar cortex.

scholarly journals Stellate cell computational modeling predicts signal filtering in the molecular layer circuit of cerebellum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martina Francesca Rizza ◽  
Francesca Locatelli ◽  
Stefano Masoli ◽  
Diana Sánchez-Ponce ◽  
Alberto Muñoz ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Stellate Cell ◽  
Molecular Layer ◽  
Stellate Cells ◽  
Parallel Fiber ◽  
Cell Discharge ◽  
Physiological Properties ◽  
Low Pass ◽  
Band Pass ◽  
Very High Frequencies

AbstractThe functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass filters. A detailed computational model summarizing these physiological properties allowed to explore different functional configurations of the parallel fiber—stellate cell—Purkinje cell circuit. Simulations showed that, following parallel fiber stimulation, Purkinje cells almost linearly increased their response with input frequency, but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass filtering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.

scholarly journals Stellate cell computational modelling predicts signal filtering in the molecular layer circuit of cerebellum

2020 ◽  
Author(s):  
Martina Francesca Rizza ◽  
Francesca Locatelli ◽  
Stefano Masoli ◽  
Diana Sánchez Ponce ◽  
Alberto Muñoz ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Stellate Cell ◽  
Molecular Layer ◽  
Computational Modelling ◽  
Stellate Cells ◽  
Parallel Fiber ◽  
Cell Discharge ◽  
Physiological Properties ◽  
Low Pass ◽  
Very High Frequencies

AbstractThe functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass filters. A detailed computational model summarizing these physiological properties allowed to explore different functional configurations of the parallel fiber – stellate cell – Purkinje cell circuit. Simulations showed that, following parallel fiber stimulation, Purkinje cells almost linearly increased their response with input frequency but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass filtering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.

scholarly journals Impact of parallel fiber to Purkinje cell long-term depression is unmasked in absence of inhibitory input

2018 ◽  
Vol 4 (10) ◽  
pp. eaas9426 ◽  
Author(s):  
Henk-Jan Boele ◽  
Saša Peter ◽  
Michiel M. Ten Brinke ◽  
Lucas Verdonschot ◽  
Anna C. H. IJpelaar ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Eyeblink Conditioning ◽  
Molecular Layer ◽  
Learning Task ◽  
Parallel Fiber ◽  
Neural Mechanisms ◽  
Inhibitory Input ◽  
Long Term Depression ◽  
Feed Forward Inhibition

Pavlovian eyeblink conditioning has been used extensively to study the neural mechanisms underlying associative and motor learning. During this simple learning task, memory formation takes place at Purkinje cells in defined areas of the cerebellar cortex, which acquire a strong temporary suppression of their activity during conditioning. Yet, it is unknown which neuronal plasticity mechanisms mediate this suppression. Two potential mechanisms include long-term depression of parallel fiber to Purkinje cell synapses and feed-forward inhibition by molecular layer interneurons. We show, using a triple transgenic approach, that only concurrent disruption of both these suppression mechanisms can severely impair conditioning, highlighting that both processes can compensate for each other’s deficits.

scholarly journals Integrative Versus Delay Line Characteristics of Cerebellar Cortex

1976 ◽  
Vol 3 (2) ◽  
pp. 85-97 ◽  
Author(s):  
W.A. MacKay ◽  
J.T. Murphy
Keyword(s):  
Cerebellar Cortex ◽  
Cell Activation ◽  
Delay Line ◽  
Granule Cells ◽  
Molecular Layer ◽  
Parallel Fiber ◽  
Response Latencies ◽  
Integrator Model ◽  
P Cells

SUMMARY:In order to determine which of two general models (“tapped delay line” or “integrator”) provides a more accurate description of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells.Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity.No evidence, therefore, was found in cat cerebellum to support the “tapped delay line” model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the “integrator” model is discussed.

Involvement of Kv1 Potassium Channels in Spreading Acidification and Depression in the Cerebellar Cortex

2005 ◽  
Vol 94 (2) ◽  
pp. 1287-1298 ◽  
Author(s):  
Gang Chen ◽  
Wangcai Gao ◽  
Kenneth C. Reinert ◽  
Laurentiu S. Popa ◽  
Claudia M. Hendrix ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Cerebellar Cortex ◽  
Molecular Layer ◽  
Neutral Red ◽  
Parallel Fiber ◽  
Null Mouse ◽  
Gabaergic Neurotransmission ◽  
Multiple Cycles

Spreading acidification and depression (SAD) is a form of propagated activity in the cerebellar cortex characterized by acidification and a transient depression in excitability. This study investigated the role of Kv1 potassium channels in SAD using neutral red, flavoprotein autofluorescence, and voltage-sensitive dye optical imaging in the mouse cerebellar cortex, in vivo. The probability of evoking SAD was greatly increased by blocking Kv1.1 as well as Kv1.2 potassium channels by their specific blockers dendrotoxin K (DTX-K) and tityustoxin (TsTX), respectively. DTX-K not only greatly lowered the threshold for evoking SAD but also resulted in multiple cycles of spread and spontaneous SAD. The occurrence of spontaneous SAD originating from spontaneous parallel fiber-like beams of activity suggests that blocking Kv1 channels increased parallel fiber excitability. This was confirmed by the generation of parallel fiber-like beams with the microinjection of glutamate into the upper molecular layer in the presence of DTX-K. The dramatic effects of DTX-K suggest a possible connection between SAD and episodic ataxia type 1 (EA1), a Kv1.1 potassium channelopathy. The threshold for evoking SAD was significantly lowered in the Kv1.1 heterozygous knockout mouse compared with wild-type littermates. Carbamazepine and acetazolamide, both effective in the treatment of EA1, significantly decreased the likelihood of evoking SAD. Blocking GABAergic neurotransmission did not alter the effectiveness of DTX-K. The cyclin D2 null mouse, which lacks cerebellar stellate cells, also exhibited SAD. Therefore blocking Kv1 potassium channels establishes the conditions needed to generate SAD. Furthermore, the results are consistent with the hypothesis that SAD may underlie the transient attacks of ataxia characterizing EA1.

Dynamics of Electrosensory Feedback: Short-Term Plasticity and Inhibition in a Parallel Fiber Pathway

2002 ◽  
Vol 88 (4) ◽  
pp. 1695-1706 ◽  
Author(s):  
John E. Lewis ◽  
Leonard Maler
Keyword(s):  
Pyramidal Neurons ◽  
Molecular Layer ◽  
Parallel Fiber ◽  
Weakly Electric Fish ◽  
Short Term ◽  
Stimulus Interval ◽  
Simple Description ◽  
Feed Forward ◽  
Synaptic Dynamics ◽  
Feed Forward Inhibition

The dynamics of neuronal feedback pathways are generally not well understood. This is due to the complexity arising from the combined dynamics of closed-loop feedback systems and the synaptic plasticity of feedback connections. Here, we investigate the short-term synaptic dynamics underlying the parallel fiber feedback pathway to a primary electrosensory nucleus in the weakly electric fish, Apteronotus leptorhynchus. In open-loop conditions, the dynamics of this pathway arise from a monosynaptic excitatory connection and a disynaptic (feed-forward) inhibitory connection to pyramidal neurons in the electrosensory lateral line lobe (ELL). In a brain slice preparation of the ELL, we characterized the synaptic responses of pyramidal neurons to short trains of electrical stimuli delivered to the parallel fibers of the dorsal molecular layer. Stimulus trains consisted of 20 pulses, at either random intervals or constant intervals, with varying mean frequencies. With random trains, pyramidal neuron responses were well described by a single exponential function of the inter-stimulus interval—suggesting a single facilitation-like process underlies these synaptic dynamics. However, responses to periodic (constant interval) trains deviated from this simple description. Random and periodic stimulus trains delivered when the feed-forward inhibitory component of this pathway was pharmacologically blocked revealed that inhibition and depression also contribute to the observed dynamics. We formulated a simple model of the parallel fiber synaptic dynamics that provided an accurate description of our data. The model dynamics resulted from a combination of three distinct processes. Two of the processes are the classically-described synaptic facilitation and depression, and the third is a novel description of feed-forward inhibition. An analysis of this model suggests that synaptic pathways combining plasticity with feed-forward inhibition can be easily tuned to signal different types of transient stimuli and thus lead to diverse and nonintuitive filtering properties.

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