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Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity.

de San Martin JZ, Jalil A, Trigo FF - J. Gen. Physiol. (2015)

Bottom Line: Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release.The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity.Finally, we show that single-site activation of presynaptic GABA(A) autoRs leads to an increase in MLI excitability and thus conveys a strong feedback signal that contributes to spiking activity.

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Affiliation: Laboratoire de Physiologie Cérébrale, Université Paris Descartes and Centre National de la Recherche Scientifique, CNRS UMR8118, 75794 Paris, France.

No MeSH data available.


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Axonal synaptic events are filtered by the axon. (A) Schematic reconstruction of an MLI that was successfully stimulated in several axonal varicosities (arrowheads; somatodendritic domain is in magenta, and axon is in green). (B) Representative traces of individual ASCs evoked in the positions indicated in A. The vertical dotted line indicates timing of the laser pulse. (C) Amplitude distribution of all the recorded ASCs (gray; n = 64 sites from 33 cells) and from four selected individual sites to illustrate the degree of intra-site variability (colored histograms and associated Gaussian fits, n = 3–12 events/site). (D) Plot of ASC amplitude as a function of the distance between the soma and the release site. Each circle represents an individual experiment; continuous black line is the exponential fit. The distance at which the amplitudes are reduced to 37% of their extrapolated maximal amplitude (D37) is 56 ± 9 µm (n = 64 sites). Gray lines are the fits of simulated datasets using different autoR synaptic conductance values. The simulation performed with a 3-nS autoR synaptic conductance best fitted experimental data (Chi2 values corresponding to the simulations with 1-, 2-, 3-, 4-, and 5-nS autoR conductance: 467.7, 174.3, 166.7, 259.6, and 395.0, respectively). (E) Plot of ASC amplitude as a function of τrise. Continuous line is the linear fit (P < 0.01; Pearson’s coefficient: −0.56; n = 23 sites). (F) Plot of ASC τdecay as a function of τrise. Continuous line is the linear fit (P > 0.05; Pearson’s coefficient: 0.02; n = 23 sites).
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fig4: Axonal synaptic events are filtered by the axon. (A) Schematic reconstruction of an MLI that was successfully stimulated in several axonal varicosities (arrowheads; somatodendritic domain is in magenta, and axon is in green). (B) Representative traces of individual ASCs evoked in the positions indicated in A. The vertical dotted line indicates timing of the laser pulse. (C) Amplitude distribution of all the recorded ASCs (gray; n = 64 sites from 33 cells) and from four selected individual sites to illustrate the degree of intra-site variability (colored histograms and associated Gaussian fits, n = 3–12 events/site). (D) Plot of ASC amplitude as a function of the distance between the soma and the release site. Each circle represents an individual experiment; continuous black line is the exponential fit. The distance at which the amplitudes are reduced to 37% of their extrapolated maximal amplitude (D37) is 56 ± 9 µm (n = 64 sites). Gray lines are the fits of simulated datasets using different autoR synaptic conductance values. The simulation performed with a 3-nS autoR synaptic conductance best fitted experimental data (Chi2 values corresponding to the simulations with 1-, 2-, 3-, 4-, and 5-nS autoR conductance: 467.7, 174.3, 166.7, 259.6, and 395.0, respectively). (E) Plot of ASC amplitude as a function of τrise. Continuous line is the linear fit (P < 0.01; Pearson’s coefficient: −0.56; n = 23 sites). (F) Plot of ASC τdecay as a function of τrise. Continuous line is the linear fit (P > 0.05; Pearson’s coefficient: 0.02; n = 23 sites).

Mentions: Fig. 4 (A and B) shows a cell in which we performed caged-Ca2+ photolysis in five different release sites; the amplitudes and kinetics of the events arising from the stimulation of the different release sites were variable (amplitudes: 15–35 pA, coefficient of variation [CV] = 0.32). The amplitude distribution of ASCs recorded across all experiments is shown in the gray histogram of Fig. 4 C; it represents a wide range of values and displays a marked skew toward large values. Each color histogram and corresponding Gaussian fit are examples of the amplitude distributions of the events evoked in single varicosities; they show that, although inter-site variability is high, intra-site variability is low, similarly to what was estimated for the inter-site variability of postsynaptic responses in individual synapses (Auger and Marty, 1997; Nusser et al., 1997). The amplitudes in individual varicosities could be described by a Gaussian distribution, and the average coefficient of variation estimated from individual sites was significantly smaller than the coefficient of variation calculated from the amplitudes corresponding to all the stimulated varicosities (CVind: 0.16 ± 0.02; n = 41 varicosities; CVall = 0.55; n = 64 sites; P < 0.0001). As an example, in the cell shown in Fig. 2, the amplitude CV of the seven laser-evoked currents was as low as 0.11. Collectively, these results suggest the existence of heterogeneities among the different release sites within a cell and between cells.


Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity.

de San Martin JZ, Jalil A, Trigo FF - J. Gen. Physiol. (2015)

Axonal synaptic events are filtered by the axon. (A) Schematic reconstruction of an MLI that was successfully stimulated in several axonal varicosities (arrowheads; somatodendritic domain is in magenta, and axon is in green). (B) Representative traces of individual ASCs evoked in the positions indicated in A. The vertical dotted line indicates timing of the laser pulse. (C) Amplitude distribution of all the recorded ASCs (gray; n = 64 sites from 33 cells) and from four selected individual sites to illustrate the degree of intra-site variability (colored histograms and associated Gaussian fits, n = 3–12 events/site). (D) Plot of ASC amplitude as a function of the distance between the soma and the release site. Each circle represents an individual experiment; continuous black line is the exponential fit. The distance at which the amplitudes are reduced to 37% of their extrapolated maximal amplitude (D37) is 56 ± 9 µm (n = 64 sites). Gray lines are the fits of simulated datasets using different autoR synaptic conductance values. The simulation performed with a 3-nS autoR synaptic conductance best fitted experimental data (Chi2 values corresponding to the simulations with 1-, 2-, 3-, 4-, and 5-nS autoR conductance: 467.7, 174.3, 166.7, 259.6, and 395.0, respectively). (E) Plot of ASC amplitude as a function of τrise. Continuous line is the linear fit (P < 0.01; Pearson’s coefficient: −0.56; n = 23 sites). (F) Plot of ASC τdecay as a function of τrise. Continuous line is the linear fit (P > 0.05; Pearson’s coefficient: 0.02; n = 23 sites).
© Copyright Policy - openaccess
Related In: Results  -  Collection

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fig4: Axonal synaptic events are filtered by the axon. (A) Schematic reconstruction of an MLI that was successfully stimulated in several axonal varicosities (arrowheads; somatodendritic domain is in magenta, and axon is in green). (B) Representative traces of individual ASCs evoked in the positions indicated in A. The vertical dotted line indicates timing of the laser pulse. (C) Amplitude distribution of all the recorded ASCs (gray; n = 64 sites from 33 cells) and from four selected individual sites to illustrate the degree of intra-site variability (colored histograms and associated Gaussian fits, n = 3–12 events/site). (D) Plot of ASC amplitude as a function of the distance between the soma and the release site. Each circle represents an individual experiment; continuous black line is the exponential fit. The distance at which the amplitudes are reduced to 37% of their extrapolated maximal amplitude (D37) is 56 ± 9 µm (n = 64 sites). Gray lines are the fits of simulated datasets using different autoR synaptic conductance values. The simulation performed with a 3-nS autoR synaptic conductance best fitted experimental data (Chi2 values corresponding to the simulations with 1-, 2-, 3-, 4-, and 5-nS autoR conductance: 467.7, 174.3, 166.7, 259.6, and 395.0, respectively). (E) Plot of ASC amplitude as a function of τrise. Continuous line is the linear fit (P < 0.01; Pearson’s coefficient: −0.56; n = 23 sites). (F) Plot of ASC τdecay as a function of τrise. Continuous line is the linear fit (P > 0.05; Pearson’s coefficient: 0.02; n = 23 sites).
Mentions: Fig. 4 (A and B) shows a cell in which we performed caged-Ca2+ photolysis in five different release sites; the amplitudes and kinetics of the events arising from the stimulation of the different release sites were variable (amplitudes: 15–35 pA, coefficient of variation [CV] = 0.32). The amplitude distribution of ASCs recorded across all experiments is shown in the gray histogram of Fig. 4 C; it represents a wide range of values and displays a marked skew toward large values. Each color histogram and corresponding Gaussian fit are examples of the amplitude distributions of the events evoked in single varicosities; they show that, although inter-site variability is high, intra-site variability is low, similarly to what was estimated for the inter-site variability of postsynaptic responses in individual synapses (Auger and Marty, 1997; Nusser et al., 1997). The amplitudes in individual varicosities could be described by a Gaussian distribution, and the average coefficient of variation estimated from individual sites was significantly smaller than the coefficient of variation calculated from the amplitudes corresponding to all the stimulated varicosities (CVind: 0.16 ± 0.02; n = 41 varicosities; CVall = 0.55; n = 64 sites; P < 0.0001). As an example, in the cell shown in Fig. 2, the amplitude CV of the seven laser-evoked currents was as low as 0.11. Collectively, these results suggest the existence of heterogeneities among the different release sites within a cell and between cells.

Bottom Line: Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release.The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity.Finally, we show that single-site activation of presynaptic GABA(A) autoRs leads to an increase in MLI excitability and thus conveys a strong feedback signal that contributes to spiking activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire de Physiologie Cérébrale, Université Paris Descartes and Centre National de la Recherche Scientifique, CNRS UMR8118, 75794 Paris, France.

No MeSH data available.


Related in: MedlinePlus