209 research outputs found
LONG-TERM PLASTICITY CHAINS IN THE CEREBELLAR CORTEX
No full textThe sites and mechanisms of long-term synaptic plasticity (LTP and LTD) in the cerebellar cortex are object of debate. What is apparently lacking is a determination of the plastic changes occurring when the whole circuit is engaged. In this way, LTP and LTD may occur at multiple sites as well as in the intrinsic excitable mechanisms of these same neurons. In particular, we have tested the impact of theta burst stimulation (TBS) delivered to the mossy fibers (Mapelli and D'Angelo, 2007).Voltage-Sensitive Dye (VSD) imaging on rat cerebellar slices showed various areas of plasticity following TBS, with a remarkable prevalence of LTD in the granular layer and of LTP in the Purkinje cell layer. At the same time, firing changes were monitored in Purkinje cells (PCs) and molecular layer interneurons (MLIs) using paired loose cell-attached (n=5) and whole-cell recordings (n=5). The PCs showed enhanced probability of response and enhanced time precision with reduced first spike delay. This could be due either to a secondary reduction of MLIs activity (which showed depression of response in the majority of cases) or to enhanced parallel fiber – Purkinje cells transmission, or both. While these mechanistic hypotheses are currently under investigation, these results already indicate that afferent patterns cause distributed plasticity in the network suggesting that chains of changes are the salient aspect to be considered in order to interpret the processes of cerebellar learning
High-pass filtering and dynamic gain regulation enhance vertical bursts transmission along the mossy fiber pathway of cerebellum
No full textSignal elaboration in the cerebellum mossy fiber input pathway presents controversial aspects, especially concerning gain regulation and the spot-like (rather than beam-like) appearance of granular-to-molecular layer transmission. By using voltage-sensitive dye (VSD) imaging in rat cerebellar slices (Mapelli et al., 2010), we found that mossy fiber bursts optimally excited the granular layer above ~50 Hz and the overlaying molecular layer above ~100 Hz, thus generating a cascade of high-pass filters. NMDA receptors enhanced transmission in the granular, while GABA-A receptors depressed transmission in both the granular and molecular layer. Burst transmission gain was controlled through a dynamic frequency-dependent involvement of these receptors. Moreover, while high-frequency transmission was enhanced along vertical lines connecting the granular to molecular layer, no high-frequency enhancement was observed along the parallel fiber axis in the molecular layer. This was probably due to the stronger effect of Purkinje cell GABA-A receptor-mediated inhibition occurring along the parallel fibers than along the granule cell axon ascending branch. The consequent amplification of burst responses along vertical transmission lines could explain the spot-like activation of Purkinje cells observed following punctuate stimulation in vivo
Editorial: Insights in cellular neurophysiology: 2022
No full textThis Research Topic invited Frontiers Editors to highlight significant challenges and recent accomplishments in the neuroscientific field and highlight future directions. Seven contributions were gathered, including original articles, a review, and a methods report
The spatial organization of long-term synaptic plasticity at the input stage of the cerebellum
No full textThe spatial organization of long-term synaptic plasticity [long-term potentiation (LTP) and long-term depression (LTD)] is supposed to play a critical role for distributed signal processing in neuronal networks, but its nature remains undetermined in most central circuits. By using multielectrode array recordings, we have reconstructed activation maps of the granular layer in cerebellar slices. LTP and LTD induced by theta-burst stimulation appeared in patches organized in such a way that, on average, LTP was surrounded by LTD. The sign of long-term synaptic plasticity in a given granular layer region was directly correlated with excitation and inversely correlated with inhibition: the most active areas tended to generate LTP, whereas the least active areas tended to generate LTD. Plasticity was almost entirely prevented by application of the NMDA receptor blocker, APV. This suggests that synaptic inhibition, through a control of membrane depolarization, effectively regulates NMDA channel unblock, postsynaptic calcium entry, and the induction of bidirectional synaptic plasticity at the mossy fiber-granule cell relay (Gall et al., 2005). By this mechanism, LTP and LTD could regulate the geometry and contrast of network computations, preprocessing the mossy fiber input to be conveyed to Purkinje cells and molecular layer interneurons
The spatio-temporal filtering hypothesis of the cerebellar cortex: evidence from VSD imaging
No full textThe functional mechanisms of the cerebellar cortex are still object of debate and it is not fully clear how mossy fiber inputs are transformed in the granular layer and retransmitted to the molecular layer and Purkinje cells. Here the spatio-temporal properties of granular-to-molecular layer transmission in response to mossy fiber bursts of different frequencies have been investigated using voltage-sensitive dye imaging. The granular layer was optimally excited above ~50 Hz and the molecular layer responded above ~100 Hz with a steep gain curve. The high-pass filtering properties depended on GABA and NMDA receptors: NMDA receptors determined mossy fiber – granular layer frequency-dependence, while GABA receptors determined granular to molecular layer frequency-dependence. Moreover, GABA receptors reduced granular layer gain through a dynamic mechanism (-103%) rather than tonic inhibition (+17%). These results indicate that the mossy fiber pathway favors bursts-burst transmission, which is dynamically controlled by the local circuitry in a frequency dependent manner
cerebellar circuit activation through the mossy fiber-parallel fiber pathway using high-resolution VSD imaging in acute cerebellar slices
No full textIt is not yet fully clear how mossy fiber inputs activate the granular layer retransmitting signals through the ascending axon and parallel fibers to Purkinje cells. We have characterized the spatio-temporal properties of cerebellar circuit activation in response to mossy fiber stimulation by using Voltage-Sensitive Dye (VSD) imaging in sagittal and coronal rat cerebellar slices (P20-P25). Fluorescent signals generated by Di4-ANNEPS were sampled at 1 KHz with a Micam-Ultima camera (SciMedia). The granular layer was activated in spots of about 30 micrometer diameter showing distinct intensities of response with delays of 2.1±0.15 ms (n=15). Then activation propagated into the molecular and Purkinje cell layers with an additional 3.6±1.1 ms delay (n=10). Simultaneous patch-clamp recordings from granule cells and Purkinje cells showed a direct correlation between intracellular depolarization and VSD signal. In sagittal slices, mossy fiber stimulation activated the overlaying area supporting vertical transmission, while in coronal slices activation also propagated laterally demonstrating spread of excitation along the parallel fibers. Transmission through the granular layer and to the molecular layer was more pronounced using high-frequency bursts rather than single isolated stimuli (+85.5%, n=8, from 0.1 Hz to 500 Hz), was markedly reduced by NMDA receptor blockers (e.g. -17.9%, n=4, at 200 Hz) and was enhanced by GABA-A receptor blockers (e.g. +36.9 %; n=4 at 200 Hz). VSD recordings reveal therefore (1) that the granular layer activates in spots depending on NMDA and GABA-A receptors, (2) that signals are transmitted toward the molecular layer depending on the frequency of the mossy fiber input and (3) that Purkinje cell excitation through the ascending granule cell axon coexist with that due to parallel fiber transmission. These observations provide the basis for a detailed investigation of spatio-temporal signal processing in the cerebellar circuit
The circuit properties of the cerebellar cortex revealed by Voltage-Sensitive Dye (VSD) imaging
No full textAlthough the cellular physiology of cerebellar neurons has made remarkable progress, the analysis of circuit functional properties is still incomplete. In order to asses theoretical predictions, we have performed VSD imaging measurements addressing three main issues. 1) VSD imaging was used to measure combinatorial responses in the cerebellum granular layer showing "combined excitation" and "combined inhibition". These depended on whether the response were enhanced or reduced, lasted for tens of ms and were regulated by synaptic inhibition. This is the first demonstration of the presence of combinatorial operations in the cerebellum. 2) VSD imaging was used to measure responses to bursts at different frequencies. Transmission through the mossy fiber–granular layer-molecular layer pathway was frequency-dependent generating a cascade of two high-pass filters regulated by NMDA and GABA-A receptors. 3) VSD imaging was used to investigate patterns transmission from the granular to molecular layer. High-frequency bursts were enhanced along vertical transmission lines but not along parallel fibers, suggesting that they could be specialized to convey low-frequency signals throughout the cerebellum. These results support the hypothesis that the mossy fiber input of the cerebellar cortex implements a complex spatio-temporal filter, in which local computations (and potentially long-term synaptic plasticity) can differentially redistribute activation among the neuronal elements
Changes of the biophysical properties of voltage-gated Na+ currents during maturation of the sodium-taste cells in rat fungiform papillae
No full textTaste cells are sensory receptors that undergo continuous turnover while they detect food chemicals and communicate with afferent nerve fibers. The voltage-gated sodium current (INa ) is a key ion current for generating action potentials in fully differentiated and chemo-sensitive taste cells, which use electrical signaling to release neurotransmitters. Here we show that, during the maturation of rat taste cells involved in salt detection (sodium cells), the biophysical properties of INa , such as voltage dependence of activation and inactivation, change significantly. Our results help understand how taste cells gain electrical excitability during turnover, a property critical to operate as chemical detectors that relay sensory information to nerve fibers
Long-Term Spatiotemporal Reconfiguration of Neuronal Activity Revealed by Voltage-Sensitive Dye Imaging in the Cerebellar Granular Layer
No full textUnderstanding the spatiotemporal organization of long-term synaptic plasticity in neuronal networks demands techniques capable of monitoring changes in synaptic responsiveness over extended multineuronal structures. Among these techniques, voltage-sensitive dye imaging (VSD imaging) is of particular interest due to its good spatial resolution. However, improvements of the technique are needed in order to overcome limits imposed by its low signal-to-noise ratio. Here, we show that VSD imaging can detect long-term potentiation (LTP) and long-term depression (LTD) in acute cerebellar slices. Combined VSD imaging and patch-clamp recordings revealed that the most excited regions were predominantly associated with granule cells (GrCs) generating EPSP-spike complexes, while poorly responding regions were associated with GrCs generating EPSPs only. The correspondence with cellular changes occurring during LTP and LTD was highlighted by a vector representation obtained by combining amplitude with time-to-peak of VSD signals. This showed that LTP occurred in the most excited regions lying in the core of activated areas and increased the number of EPSP-spike complexes, while LTD occurred in the less excited regions lying in the surround. VSD imaging appears to be an efficient tool for investigating how synaptic plasticity contributes to the reorganization of multineuronal activity in neuronal circuits
Combinatorial responses controlled by synaptic inhibition in the cerebellum granular layer
No full textThe granular layer of cerebellum has been long hypothesized to perform combinatorial operations on incoming signals. Although this assumption is at the basis of main computational theories of cerebellum, it has never been assessed experimentally. Here, by applying high-resolution voltage-sensitive dye imaging techniques, we show that simultaneous activation of two partially overlapping mossy fiber bundles (either with single pulses or high-frequency bursts) can cause combined excitation and combined inhibition, which are compatible with the concepts of coincidence detection and spatial pattern separation predicted by theory. Combined excitation appeared as an area in which the combination of two inputs is greater than the arithmetic sum of the individual inputs and was enhanced by gamma-aminobutyric acid type A (GABA(A)) receptor blockers. Combined inhibition was manifest as an area where two inputs combined resulted in a reduction to less than half of the activity evoked from either one of the two inputs alone and was prevented by GABA(A) receptor blockers. The combinatorial responses occupied small granular layer regions (approximately 30 microm diameter), with combined inhibition being interspersed among extended areas of combined excitation. Moreover, the combinatorial effects lasted for tens of milliseconds and combined inhibition occurred only after termination of the stimuli. These combinatorial operations, if engaged by natural input patterns in vivo, may be important to influence incoming impulses organizing spatiotemporal spike sequences to be relayed to Purkinje cell
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