nmda receptor blocker l 689 560  (Tocris)

Journal: Nature Communications

Article Title: Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

doi: 10.1038/s41467-021-22893-8

Figure Lengend Snippet: a Schematics of cerebellar circuit. b UMAP embedding showing normalized expression of gene involved in mGluR1 signaling cascade. c Same as in b for AMPA and NMDA receptors. d Same as in b for genes involved in mGluR2/3 signaling cascade. e Example spiking responses in different UBCs to a burst of MF input (20 stimuli at 100 Hz). f Instantaneous firing rate for the same cells.

Article Snippet: Sequential drug wash-ins were performed using a computer-controlled solenoid manifold system (ValveLink 8.2, Automate Scientific, Inc., Berkeley, CA) with a flow rate of 1 to 2 mL/min, where indicated, with mGluR1 antagonist (100 µM LY357385, Tocris Bio-Techne, Minneapolis, MN), AMPA receptor blocker (5 µM NBQX), NMDA receptor blocker (2 µM R-CPP), mGluR2/3 antagonist (1 µM LY341495, Tocris Bio-Techne, Minneapolis, MN) and DGK inhibitor II (100 µM R59949, MilliporeSigma, St. Louis, MO)

Techniques: Expressing

Journal: Nature Communications

Article Title: Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

doi: 10.1038/s41467-021-22893-8

Figure Lengend Snippet: a Examples of instantaneous firing rate from on-cell recordings before (black) and after (gray) the application of AMPA/NMDA receptor antagonist (gray bar) in a fast (left) and a slow (right) UBC. Each trace is an average of 8 trials. b Summary of evoked spiking (20 × 100 Hz) and the effect of AMPA/NMDA receptor antagonist (normalized to baseline, mean ± sem, n = 5). c Examples of instantaneous firing rate from on-cell recordings before (black) and after (red) the application of an mGluR1 antagonist (red bar) in a fast (left) and a slow (right) UBC. Each trace is an average of 8 trials. d Summary of evoked spiking (20 × 100 Hz) and the effect of an mGluR1 antagonist (normalized to baseline, mean±sem, n = 5). e Example of instantaneous firing rate before and after 20 minutes of DGK inhibitor II wash-in. f Summary of half-decay time of instantaneous firing rate response with DGK inhibitor II (normalized to baseline, mean ± sem, n = 6). g Summary of peak amplitude of instantaneous firing rate response with DGK inhibitor II (normalized to baseline, mean±sem, n = 6).

Article Snippet: Sequential drug wash-ins were performed using a computer-controlled solenoid manifold system (ValveLink 8.2, Automate Scientific, Inc., Berkeley, CA) with a flow rate of 1 to 2 mL/min, where indicated, with mGluR1 antagonist (100 µM LY357385, Tocris Bio-Techne, Minneapolis, MN), AMPA receptor blocker (5 µM NBQX), NMDA receptor blocker (2 µM R-CPP), mGluR2/3 antagonist (1 µM LY341495, Tocris Bio-Techne, Minneapolis, MN) and DGK inhibitor II (100 µM R59949, MilliporeSigma, St. Louis, MO)

Techniques:

Journal: Nature Communications

Article Title: Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

doi: 10.1038/s41467-021-22893-8

Figure Lengend Snippet: a Sample cell-attached recording (top) instantaneous firing rate (middle) and synaptic current measured with whole-cell voltage clamp (bottom) in a cell with fast response. b Same as in a but for a cell with intermediate speed response. c Same as in a but for a cell with clear biphasic synaptic current (bottom). d Same as in a but for a cell with slow biphasic response. e Same as in a but for a cell with only a pause in firing. f Half-decay times of firing rates vs. half-decay times of currents and linear fit on a log-log plot ( R adj 2 = 0.91, slope = 0.88, intercept = −0.22, n = 17). g Peak firing rate vs. peak current amplitude and linear fit on a log-log plot ( R adj 2 = 0.69, slope = 0.71, intercept = −0.65, n = 17). h Pause duration vs. amplitude of the current at stimulation offset, and linear fit with log 10 response variable (black, R adj 2 = 0.44, slope = 0.01, intercept = −0.42, n = 20). i Heatmap of peak normalized mGluR1-mediated current ( n = 10). j Heatmap of peak normalized mGluR2/3-mediated current ( n = 7). k Average synaptic response before (black), after (red) mGluR1 antagonist, and after AMPA/NMDA receptor antagonist wash-ins (gray). Each trace is an average of 8 trials. l Average synaptic response before (top, black) and after (top, blue) mGluR2/3 antagonist wash-in, and their difference (bottom, black). Each trace is an average of 8 trials.

Article Snippet: Sequential drug wash-ins were performed using a computer-controlled solenoid manifold system (ValveLink 8.2, Automate Scientific, Inc., Berkeley, CA) with a flow rate of 1 to 2 mL/min, where indicated, with mGluR1 antagonist (100 µM LY357385, Tocris Bio-Techne, Minneapolis, MN), AMPA receptor blocker (5 µM NBQX), NMDA receptor blocker (2 µM R-CPP), mGluR2/3 antagonist (1 µM LY341495, Tocris Bio-Techne, Minneapolis, MN) and DGK inhibitor II (100 µM R59949, MilliporeSigma, St. Louis, MO)

Techniques:

Journal: Nature Communications

Article Title: Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

doi: 10.1038/s41467-021-22893-8

Figure Lengend Snippet: a Schematics of cerebellar circuit. b UMAP embedding showing normalized expression of gene involved in mGluR1 signaling cascade. c Same as in b for AMPA and NMDA receptors. d Same as in b for genes involved in mGluR2/3 signaling cascade. e Example spiking responses in different UBCs to a burst of MF input (20 stimuli at 100 Hz). f Instantaneous firing rate for the same cells.

Article Snippet: Sequential drug wash-ins were performed using a computer-controlled solenoid manifold system (ValveLink 8.2, Automate Scientific, Inc., Berkeley, CA) with a flow rate of 1 to 2 mL/min, where indicated, with mGluR1 antagonist (100 μM LY357385, Tocris Bio-Techne, Minneapolis, MN), AMPA receptor blocker (5 μM NBQX), NMDA receptor blocker (2 μM R-CPP), mGluR2/3 antagonist (1 μM LY341495, Tocris Bio-Techne, Minneapolis, MN) and DGK inhibitor II (100 μM R59949, MilliporeSigma, St. Louis, MO)

Techniques: Expressing

Journal: Nature Communications

Article Title: Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

doi: 10.1038/s41467-021-22893-8

Figure Lengend Snippet: a Examples of instantaneous firing rate from on-cell recordings before (black) and after (gray) the application of AMPA/NMDA receptor antagonist (gray bar) in a fast (left) and a slow (right) UBC. Each trace is an average of 8 trials. b Summary of evoked spiking (20 × 100 Hz) and the effect of AMPA/NMDA receptor antagonist (normalized to baseline, mean ± sem, n = 5). c Examples of instantaneous firing rate from on-cell recordings before (black) and after (red) the application of an mGluR1 antagonist (red bar) in a fast (left) and a slow (right) UBC. Each trace is an average of 8 trials. d Summary of evoked spiking (20 × 100 Hz) and the effect of an mGluR1 antagonist (normalized to baseline, mean±sem, n = 5). e Example of instantaneous firing rate before and after 20 minutes of DGK inhibitor II wash-in. f Summary of half-decay time of instantaneous firing rate response with DGK inhibitor II (normalized to baseline, mean ± sem, n = 6). g Summary of peak amplitude of instantaneous firing rate response with DGK inhibitor II (normalized to baseline, mean±sem, n = 6).

Article Snippet: Sequential drug wash-ins were performed using a computer-controlled solenoid manifold system (ValveLink 8.2, Automate Scientific, Inc., Berkeley, CA) with a flow rate of 1 to 2 mL/min, where indicated, with mGluR1 antagonist (100 μM LY357385, Tocris Bio-Techne, Minneapolis, MN), AMPA receptor blocker (5 μM NBQX), NMDA receptor blocker (2 μM R-CPP), mGluR2/3 antagonist (1 μM LY341495, Tocris Bio-Techne, Minneapolis, MN) and DGK inhibitor II (100 μM R59949, MilliporeSigma, St. Louis, MO)

Techniques:

Journal: Nature Communications

Article Title: Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells

doi: 10.1038/s41467-021-22893-8

Figure Lengend Snippet: a Sample cell-attached recording (top) instantaneous firing rate (middle) and synaptic current measured with whole-cell voltage clamp (bottom) in a cell with fast response. b Same as in a but for a cell with intermediate speed response. c Same as in a but for a cell with clear biphasic synaptic current (bottom). d Same as in a but for a cell with slow biphasic response. e Same as in a but for a cell with only a pause in firing. f Half-decay times of firing rates vs. half-decay times of currents and linear fit on a log-log plot ( R adj 2 = 0.91, slope = 0.88, intercept = −0.22, n = 17). g Peak firing rate vs. peak current amplitude and linear fit on a log-log plot ( R adj 2 = 0.69, slope = 0.71, intercept = −0.65, n = 17). h Pause duration vs. amplitude of the current at stimulation offset, and linear fit with log 10 response variable (black, R adj 2 = 0.44, slope = 0.01, intercept = −0.42, n = 20). i Heatmap of peak normalized mGluR1-mediated current ( n = 10). j Heatmap of peak normalized mGluR2/3-mediated current ( n = 7). k Average synaptic response before (black), after (red) mGluR1 antagonist, and after AMPA/NMDA receptor antagonist wash-ins (gray). Each trace is an average of 8 trials. l Average synaptic response before (top, black) and after (top, blue) mGluR2/3 antagonist wash-in, and their difference (bottom, black). Each trace is an average of 8 trials.

Article Snippet: Sequential drug wash-ins were performed using a computer-controlled solenoid manifold system (ValveLink 8.2, Automate Scientific, Inc., Berkeley, CA) with a flow rate of 1 to 2 mL/min, where indicated, with mGluR1 antagonist (100 μM LY357385, Tocris Bio-Techne, Minneapolis, MN), AMPA receptor blocker (5 μM NBQX), NMDA receptor blocker (2 μM R-CPP), mGluR2/3 antagonist (1 μM LY341495, Tocris Bio-Techne, Minneapolis, MN) and DGK inhibitor II (100 μM R59949, MilliporeSigma, St. Louis, MO)

Techniques: