Journal: Cerebral cortex (New York, N.Y. : 1991)

Article Title: Asymmetric synaptic depression in cortical networks.

doi: 10.1093/cercor/bhm119

Figure Lengend Snippet: Figure 1. (A) Schematic diagram of a simple recurrent model. The excitatory population E is connected to itself through recurrent excitatory connections (Wee) and to the inhibitory population I through inhibitory connections (Wei). The inhibitory population I is connected to itself through recurrent inhibitory connections (Wii) and to the excitatory population through excitatory connections (Wie). Open circles: excitatory connections; filled circles: inhibitory connections. (B) Asymmetric synaptic depression (b [ a) causes a larger decrease of the gain of inhibitory responses than excitatory responses. When a[b, there is a smaller decrease of the gain of inhibitory responses than the gain of excitatory responses. Parameter values were Wee 5 3.3, Wei 5 4.8, Wie 5 4.4, Wii 5 6; Fi 5 kFe (k 5 0.45). These values were chosen such that to ensure the stability of both the undepressed and depressed model equations. However, the results hold for a wide range of parameters (cf. Materials and Methods). The depression coefficients were a 5 0.3 and b 5 0.9. The gray area represents the area in which the recurrent model does not have stable and positive solutions. (C) Asymmetric synaptic depression leads to a larger reduction of inhibitory responses relative to excitatory ones, whereas symmetric synaptic depression (a 5 b) leads to a similar decrease of excitatory and inhibitory responses. Red: excitatory responses; blue: inhibitory responses.

Article Snippet: Thus, it has been proposed that synaptic depression makes each excitatory synapse relatively independent of the presynaptic responses, thus increasing neuronal sensitivity to changes in stimulus features (Abbott et al. 1997; Nelson and Turrigiano 1998).

Techniques:

Journal: Cerebral cortex (New York, N.Y. : 1991)

Article Title: Asymmetric synaptic depression in cortical networks.

doi: 10.1093/cercor/bhm119

Figure Lengend Snippet: Figure 2. Emergent properties of a simple recurrent model with asymmetric synaptic depression. (A) An extension of the model illustrated in Figure 1A. Cortical neuron E9 receives excitatory (E) and inhibitory (I) local cortical inputs via depressing synapses. The rectangle marks the recurrent circuit represented in Figure 1A. (B) Asymmetric synaptic depression causes an increase in response E9 only when the decrease in the gain of inhibitory inputs exceeds the decrease in the gain of excitatory inputs by a fixed supraunitary threshold (cf. Materials and Methods). The excitatory and inhibitory response gains were varied by increasing parameter a between 0.3 and 0.54 while keeping b fixed at 0.85. The synaptic connections between neurons E--E9 and I--E9 were We 5 3 and Wi 5 3.75. (C) Asymmetric synaptic depression causes an increase in the activity of excitatory cortical neurons (E9) that receive asymmetrically reduced excitatory and inhibitory inputs. Black line: neuronal response without depression; gray line: neuronal response after asymmetric synaptic depression; dashed line: neuronal response after symmetric synaptic depression. The changes in responses are examined for a range of input levels (Fe). The synaptic connections between neurons E--E9 and I--E9 were similar to those in panel B.

Article Snippet: Thus, it has been proposed that synaptic depression makes each excitatory synapse relatively independent of the presynaptic responses, thus increasing neuronal sensitivity to changes in stimulus features (Abbott et al. 1997; Nelson and Turrigiano 1998).

Techniques: Activity Assay

Journal: Cerebral cortex (New York, N.Y. : 1991)

Article Title: Asymmetric synaptic depression in cortical networks.

doi: 10.1093/cercor/bhm119

Figure Lengend Snippet: Figure 4. Spatial profile of intracortical excitatory and inhibitory connection strengths. Excitatory synapses (Wee and Wie) are weaker and narrower than inhibitory synapses (Wei and Wii).

Article Snippet: Thus, it has been proposed that synaptic depression makes each excitatory synapse relatively independent of the presynaptic responses, thus increasing neuronal sensitivity to changes in stimulus features (Abbott et al. 1997; Nelson and Turrigiano 1998).

Techniques:

Journal: Cerebral cortex (New York, N.Y. : 1991)

Article Title: Asymmetric synaptic depression in cortical networks.

doi: 10.1093/cercor/bhm119

Figure Lengend Snippet: Figure 5. Adaptation effects in model orientation-selective V1 neurons. (A) Synaptic strength decreases as a function of presynaptic firing rate. The depression factor of excitatory synapses was larger than that of inhibitory synapses. The results in (B)--(H) were obtained after 500 ms of continuous adaptation to a stimulus oriented at 9 (presented at maximum contrast). (B) Relative decrease in synaptic strength after adaptation. For each presynaptic neuron, we computed the mean relative reduction of inhibitory and excitatory synaptic strengths. Red points mark synapses targeting excitatory cells, whereas blue points mark synapses targeting inhibitory cells. The fact that all the points lie above the diagonal indicate that excitatory synapses exhibit stronger depression than inhibitory synapses. (C) Adaptation effects in a representative population of neurons. The adapting stimulus is marked by the red arrow. Postadaptation orientation tuning curves (red) showed a repulsive shift away from the adapting stimulus orientation. Response magnitude decreased on the near flank and increased on the far flank. (D) Changes in preferred orientation after adaptation for the population of cells. The postadaptation repulsive shift in preferred orientation is largest when the adapting stimulus is approximately 10 away from the cell’s optimal orientation. The preferred orientation was computed from the responses to the full orientation range (0--180) using the vector averaging method (cf. Dragoi et al. 2000, 2001, 2002). (E) Postadaptation change in the excitatory and inhibitory inputs to the cell with preferred orientation 0 in the asymmetric synaptic depression model. The cell is stimulated for 200 ms with 60 equally spaced orientations spanning 90 to þ90 (represented on the x- axis), and the steady-state response is represented on the y-axis. The excitatory/inhibitory inputs were computed as the sum of all the weighted excitatory/inhibitory responses that contributed to the cell’s membrane voltage. There is a decrease in inhibition and a resultant increase in excitation for stimuli between 50 and 22, which is the orientation range for which the far-flank responses are increased. (F) Postadaptation change in the excitatory and inhibitory inputs to the cell with preferred orientation 0 in the symmetric synaptic depression model. Whereas excitatory inputs decrease after adaptation, inhibitory inputs remained unchanged. (G) The ratio of the inhibitory and excitatory gain change (DGi/DGe) is significantly greater than 1 only for those input stimuli that cause far-flank response facilitation. Red curve represents the results obtained with the asymmetric depression model; blue curve represents the results obtained with the symmetric depression model. (H) The far-flank response increase of one representative neuron (tuned to 0) occurs only when the gain change of inhibitory inputs is significantly greater than that of excitatory inputs. Each dot represents the % far-flank response increase after adaptation as a function of the gain ratio DGi/DGe shown in panel G. The far-flank response increase was computed (in steps of 3) for each stimulus orientation that elicited a positive response from the 0 neuron (orientation range 36 to 36). The vertical dashed line represents the threshold above which the postadaptation far-flank responses are increased.

Article Snippet: Thus, it has been proposed that synaptic depression makes each excitatory synapse relatively independent of the presynaptic responses, thus increasing neuronal sensitivity to changes in stimulus features (Abbott et al. 1997; Nelson and Turrigiano 1998).

Techniques: Plasmid Preparation, Membrane, Inhibition

Journal: Cerebral cortex (New York, N.Y. : 1991)

Article Title: Asymmetric synaptic depression in cortical networks.

doi: 10.1093/cercor/bhm119

Figure Lengend Snippet: Figure 8. Exploring the strength of adaptation effects using a model that incorporates synaptic facilitation. The x-axis represents the percentage of excitatory synapses to inhibitory neurons that exhibit facilitation. The primary y-axis represents the postadaptation shift in preferred orientation (positive numbers indicate repulsive shifts); the secondary y-axis represents the postadaptation change in far-flank response magnitude. The adapting orientation is 9 and the adaptation effects have been measured in the neuron that showed the maximum postadaptation effects (the neuron tuned to 15).

Article Snippet: Thus, it has been proposed that synaptic depression makes each excitatory synapse relatively independent of the presynaptic responses, thus increasing neuronal sensitivity to changes in stimulus features (Abbott et al. 1997; Nelson and Turrigiano 1998).

Techniques:

Journal: bioRxiv

Article Title: Ca 2+ -dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

doi: 10.1101/2024.04.24.590962

Figure Lengend Snippet: (A) Representative confocal images showing colocalization of PDE1B immunoreactivity with D2-eGFP fluorescence (top) and with D1-tdTomato fluorescence (bottom). Scale bar is 20 μm. (B) A 10-min application of PDE1i induced persistent LTD at corticostriatal glutamatergic synapses (n = 7 neurons from 5 mice). In this panel and panels (C-G), normalized EPSC amplitudes are plotted over time and error bars indicate SEM. (C) A less selective PDE1 inhibitor 8MM-IBMX (10 μM), like AF64196, causes synaptic depression at corticostriatal glutamatergic synapses in SPNs (n = 8 neurons from 8 mice). (D) Synaptic depression could be induced by PDE1i when EPSCs were evoked by electrical stimulation with a concentric bipolar electrode placed at Layer 5 of overlaying cortex (n = 6 neurons from 6 mice). (E) Normalized paired-pulse ratio (PPR) of electrically evoked EPSCs was not significantly changed by PDE1i application. (F) Blocking cholinergic signaling with nicotinic antagonist mecamylamine (mec, 10 μM) and muscarinic antagonist scopolamine (sco, 10 μM) did not prevent PDE1i-LTD (n = 7 neurons from 4 mice). (G) Inhibition of PDE2 with Bay 60-7550 (Bay, 40 nM) did not prevent PDE1i-LTD (n = 6 neurons from 3 mice).

Article Snippet: For studying synaptic responses at corticostriatal synapses, 0.15 μL AAV5-hSyn-hChR2(H134R)-EYFP (Addgene #26973) was injected into the M1 motor cortex at the following coordinates (mm relative to Bregma): ML 1.60, AP 1.15, DV 1.55.

Techniques: Fluorescence, Blocking Assay, Inhibition

Journal: bioRxiv

Article Title: Ca 2+ -dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

doi: 10.1101/2024.04.24.590962

Figure Lengend Snippet: (A) Representative image of ChR2 expression in the parafascicular nucleus (PFN) of Grp-KH288 Cre mouse injected with Cre-off ChR2-eYFP. Scale bar is 0.5 mm. (B) Schematic diagram of the recording configuration. Whole-cell patch clamp recordings were made from SPNs in acute brain slices of Grp-KH288 Cre mice injected with Cre-off ChR2-eYFP. EPSCs were optogenetically evoked with brief blue LED pulses. (C) Left, PDE1i induces similar depression of EPSC at PFN-DLS synapses (n = 6 neurons from 4 animals) and Ctx-DLS synapses (fitted line, n=12). Right, sample EPSC traces before and 30 min after PDE1 inhibition. Scale bars are 100 pA x 20 ms. (D) Box plot summary of data in (C) showing changes in oEPSC from the last 5 min of recordings. (E) Representative confocal images showing lack of PDE1B immunoreactivity in ChIs labeled by tdTomato fluorescence (ChAT-tdT) in ChAT-Cre x Ai14 mice. Scale bar is 20 μm. (F) Schematic showing the modulation of NO-cGMP signaling in SPNs by PDE1i and downstream effect at corticostriatal and thalamostriatal synapses. CLN, centrolateral nucleus of the thalamus.

Article Snippet: For studying synaptic responses at corticostriatal synapses, 0.15 μL AAV5-hSyn-hChR2(H134R)-EYFP (Addgene #26973) was injected into the M1 motor cortex at the following coordinates (mm relative to Bregma): ML 1.60, AP 1.15, DV 1.55.

Techniques: Expressing, Injection, Patch Clamp, Inhibition, Labeling, Fluorescence

Journal: bioRxiv

Article Title: Ca 2+ -dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

doi: 10.1101/2024.04.24.590962

Figure Lengend Snippet: (A) Schematic depicting the Ca 2+ imaging assay. Left, a dSPN was patched in the whole-cell configuration, dialyzed with Ca 2+ -insensitive Alexa Fluor-568 and Ca 2+ -sensitive Fluo-4. Dendritic Ca 2+ transients were triggered by somatic depolarization (from -60 mV to -40 mV for 1 s) through the patch pipette. Two-photon line-scan imaging was performed at segments of dendrites ∼45 µm from the soma (indicated by the green box). Right, a high-magnification image of a segment of dendrite. Line scan was indicated by the green line. Scale bars, 20 μm (left) and 2 μm (right). (B) Examples of dendritic Ca 2+ transients before and after application of isradipine (2 μM) in wildtype siblings or Cacna1d G 407 R/+ mice were temporally aligned with the voltage step protocol. (C) Box plot summary of isradipine-sensitive component of dendritic Ca 2+ transient in wildtype and Cacna1d G 407 R/+ mice (both n = 10 cells from 4 mice). G407R mutation significantly increases depolarization-evoked Ca 2+ transients in the dendrites. **p = 0.0011, Mann-Whitney test. (D) Representative confocal image of ChR2 expression in the motor cortex of D1-tdTomato mouse. Scale bar is 1 mm. (E) SNAP-LTD is impaired in Cacna1d G 407 R/+ mice. EPSC was evoked by wide-field blue LED illumination (0.3 ms). LTD was induced by bath application of SNAP (5 μM) for 5 min (indicated by the grey vertical bar). Plot shows EPSC amplitude as a function of time. Data are mean ± SEM. n = 8 dSPNs from 6 wildtype mice and n = 6 dSPNs from 4 Cacna1d G 407 R/+ mice. Scale bars in (E), (G) and (I) are 200 pA x 20 ms. (F) Box plot summary of LTD amplitudes from the last 10 min of recordings shown in (E). In Cacna1d G407R/+ mice, SNAP-induced LTD was significantly impaired. **p < 0.01, Mann-Whitney test. (G) PDE1i-LTD is normal in Cacna1d G 407 R/+ mice. Plot shows EPSC amplitudes as a function of time. Data are mean ± SEM. Both n = 7 neurons from 4 animals. (H) Box plot summary of PDE1i-LTD recordings shown in (G). PDE1i induced similar synaptic depression at corticostriatal glutamatergic synapses in Cacna1d G 407 R/+ mice and interleaved wildtype littermates. n.s. not statistically significant, Mann-Whitney test. (I) DHPG-LTD is similar in wildtype and Cacna1d G 407 R/+ mice. Here, DHPG-LTD was induced by DHPG (50 μM) application for 10 min (indicated by the grey vertical bar) at a holding potential of -60 mV in the presence of 1.2 mM Ca 2+ in the bath solution. Data are mean ± SEM. Both n = 7 dSPNs from 5 mice. See also . (J) Box plot summary of LTD amplitudes from the last 10 min of recordings shown in (I). The near-threshold DHPG-LTD protocol induced similar synaptic depression in wildtype and Cacna1d G 407 R/+ mice. n.s. not statistically significant, Mann-Whitney test. (K) Schematic showing that abnormal activity of the CaV1.3-PDE1 signaling pathway in the SPNs of Cacna1d G407R/+ mice impairs postsynaptic LTD.

Article Snippet: For studying synaptic responses at corticostriatal synapses, 0.15 μL AAV5-hSyn-hChR2(H134R)-EYFP (Addgene #26973) was injected into the M1 motor cortex at the following coordinates (mm relative to Bregma): ML 1.60, AP 1.15, DV 1.55.

Techniques: Imaging, Transferring, Mutagenesis, MANN-WHITNEY, Expressing, Activity Assay

Journal: bioRxiv

Article Title: Ca 2+ -dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

doi: 10.1101/2024.04.24.590962

Figure Lengend Snippet: (A) PDE1 inhibition fails to induce synaptic depression at corticostriatal synapses in iSPNs of 6-OHDA lesioned mice (n = 6 neurons from 3 mice). In panels (A-C), time course data represented as mean ± SEM are shown on the left. Sample EPSC traces before PDE1i application and from the last 5 min of recording are shown on the right. Scale bars are 100 pA x 20 ms. (B) SNAP-LTD is intact in iSPNs of 6-OHDA lesioned mice (n = 6 neurons from 4 mice). (C) In the presence of D1R/D5R-type agonist SKF 81297 (3 μM) and mAChR antagonist scopolamine (10 μM), PDE1i-LTD is restored (n = 7 neurons from 4 mice). (D) Box plot summary of data in (A-C) showing changes in oEPSC from the last 5 min of recordings. *p < 0.05, Mann-Whitney test. (E) Two-photon image of a low-threshold spiking interneuron (LTSI) in slices from NPY-EGFP mice recorded in cell-attached mode. Scale bar, 20 μm. (F) Left, examples of cell-attached recordings from LTSIs in slices from control or 6-OHDA lesioned NPY-EGFP mice. Right, box plot summary of firing rates of LTSIs (control, n = 7 neurons from 3 mice; 6-OHDA lesioned, n = 18 neurons from 4 mice). *p < 0.05, Mann-Whitney test. (G) Left, examples of cell-attached recordings from LTSIs from 6-OHDA lesioned NPY-EGFP mice before and after application of SKF 81297 and scopolamine (n = 6 neurons from 3 mice). Right, box plot summary of LTSI firing frequency in lesioned mice before and after application of D1-type agonist and mAChR antagonist. *p < 0.05, Wilcoxon test. (H) Schematic showing that in parkinsonian mice, lack of D5R signaling and enhanced mAChR signaling lead to reduction in endogenous NO release and postsynaptic LTD.

Article Snippet: For studying synaptic responses at corticostriatal synapses, 0.15 μL AAV5-hSyn-hChR2(H134R)-EYFP (Addgene #26973) was injected into the M1 motor cortex at the following coordinates (mm relative to Bregma): ML 1.60, AP 1.15, DV 1.55.

Techniques: Inhibition, MANN-WHITNEY, Control