Source Paper
Long-term synaptic depression in the striatum: physiological and pharmacological characterization
P Calabresi, R Maj, A Pisani, NB Mercuri, G Bernardi
Journal of Neuroscience • 1992
Source Paper
P Calabresi, R Maj, A Pisani, NB Mercuri, G Bernardi
Journal of Neuroscience • 1992
The effect of tetanic activation of corticostriatal glutamatergic fibers was studied in striatal slices by utilizing extracellular and intracellular recording techniques. Tetanic stimulation produced a long- term synaptic depression (LTD) (> 2 h) of both extracellularly recorded field potentials and intracellularly recorded EPSPs. LTD was not coupled with changes of intrinsic membrane properties of the recorded neurons. In some neurons, repetitive cortical activation produced a short-term posttetanic potentiation (1–3 min). Subthreshold tetanic stimulation, which under control condition did not cause LTD, induced LTD when associated with membrane depolarization. Moreover, LTD was not expressed in cells in which the conditioning tetanus was coupled with hyperpolarization of the membrane. Bath application of aminophosphonovalerate (30–50 microM), an antagonist of NMDA receptors, did not affect the amplitude of the synaptic potentials and the expression of LTD. Striatal LTD was significantly reduced by the pretreatment of the slices with 30 microM 2-amino-3-phosphonopropionic acid, an antagonist of glutamate metabotropic receptors. LTD was not blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. Scopolamine (3 microM), an antagonist of muscarinic receptors, induced a slight, but significant, increase of the amplitude of LTD. Both SCH 23390 (3 microM), an antagonist of D1 dopamine (DA) receptors, and I- sulpiride (1 microM), an antagonist of D2 DA receptors, blocked LTD. LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine. In DA-depleted slices, LTD could be restored by applying exogenous DA (30 microM) before the conditioning tetanus. In DA-depleted slices, LTD could also be restored by coadministration of SKF 38393 (3–10 microM), a D1 receptor agonist, and of LY 171555 (1–3 microM), a D2 receptor agonist. Application of a single class of DA receptor agonists failed to restore LTD. These data show that striatal LTD requires three main physiological and pharmacological conditions: (1) membrane depolarization and action potential discharge of the postsynaptic cell during the conditioning tetanus, (2) activation of glutamate metabotropic receptors, and (3) coactivation of D1 and D2 DA receptors. Striatal LTD may alter the output signals from the striatum to the other structures of the basal ganglia. This form of synaptic plasticity can influence the striatal control of motor activity.
Objective: Create a unilateral nigrostriatal dopamine lesion via 6-hydroxydopamine injection to produce dopamine-depleted striatal slices for testing long-term synaptic depression (LTD) restoration
This is a 6-Hydroxydopamine Nigrostriatal Lesion protocol using rat as the model organism. The procedure involves 7 procedural steps, 4 equipment items, 4 materials. Extracted from a 1992 paper published in Journal of Neuroscience.
Model and subjects
rat • Not specified • Not specified • Not specified • Not specified • Not specified
Study window
~4 hours hands-on
Core workflow
Unilateral nigral injection of 6-hydroxydopamine • Prepare striatal slices • Set up extracellular and intracellular recordings
Primary readouts
Key equipment and reagents
Verified items
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Perform unilateral injection of 6-hydroxydopamine into the substantia nigra to lesion the nigrostriatal dopamine system
Note: This creates dopamine-depleted striatal slices for subsequent testing
“LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine”
Prepare striatal slices from lesioned rats for electrophysiological recording
Note: Slices should be from dopamine-depleted striatum following 6-hydroxydopamine lesion
“slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine”
Position extracellular and intracellular recording electrodes in striatal slices to measure field potentials and EPSPs
Note: Both recording techniques used simultaneously
“The effect of tetanic activation of corticostriatal glutamatergic fibers was studied in striatal slices by utilizing extracellular and intracellular recording techniques”
Apply exogenous dopamine at 30 microM concentration to dopamine-depleted slices before conditioning tetanus
Note: This restores LTD expression in dopamine-depleted slices
“In DA-depleted slices, LTD could be restored by applying exogenous DA (30 microM) before the conditioning tetanus”
Coadminister SKF 38393 (D1 agonist, 3-10 microM) and LY 171555 (D2 agonist, 1-3 microM) to dopamine-depleted slices
Note: Both agonists must be applied together; single class of agonist alone fails to restore LTD
“In DA-depleted slices, LTD could also be restored by coadministration of SKF 38393 (3–10 microM), a D1 receptor agonist, and of LY 171555 (1–3 microM), a D2 receptor agonist. Application of a single class of DA receptor agonists failed to restore LTD”
Apply tetanic stimulation to corticostriatal glutamatergic fibers to induce LTD
Note: Tetanic stimulation produces LTD lasting greater than 2 hours
“Tetanic stimulation produced a long-term synaptic depression (LTD) (> 2 h) of both extracellularly recorded field potentials and intracellularly recorded EPSPs”
Monitor and record field potentials and EPSPs to measure LTD expression following tetanic stimulation
Note: LTD is absent in dopamine-depleted slices but restored by dopamine or combined D1/D2 agonist application
“LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Create a unilateral nigrostriatal dopamine lesion via 6-hydroxydopamine injection to produce dopamine-depleted striatal slices for testing long-term synaptic depression (LTD) restoration
Objective
Create a unilateral nigrostriatal dopamine lesion via 6-hydroxydopamine injection to produce dopamine-depleted striatal slices for testing long-term synaptic depression (LTD) restoration
Subjects
From paperrat • Not specified • Not specified • Not specified • Not specified
Sample count
From paperNot specified
Cohort notes
From paperUnilateral nigral injection procedure performed
Unilateral nigral injection of 6-hydroxydopamine (Not specified)
Prepare striatal slices (Not specified)
Set up extracellular and intracellular recordings (Not specified)
Apply exogenous dopamine to restore LTD (Not specified)
Presence or absence of long-term synaptic depression (LTD) in dopamine-depleted striatal slices
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Amplitude of extracellularly recorded field potentials
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Amplitude of intracellularly recorded EPSPs
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Duration of LTD expression (greater than 2 hours)
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Presence or absence of long-term synaptic depression (LTD) in dopamine-depleted striatal slices
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Amplitude of extracellularly recorded field potentials
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Amplitude of intracellularly recorded EPSPs
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Duration of LTD expression (greater than 2 hours)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified
Scoring or quantification
Quantify the primary readouts for this experiment: Presence or absence of long-term synaptic depression (LTD) in dopamine-depleted striatal slices; Amplitude of extracellularly recorded field potentials; Amplitude of intracellularly recorded EPSPs; Duration of LTD expression (greater than 2 hours).
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Presence or absence of long-term synaptic depression (LTD) in dopamine-depleted striatal slices, Amplitude of extracellularly recorded field potentials, Amplitude of intracellularly recorded EPSPs, Duration of LTD expression (greater than 2 hours).
Source links and direct wording from the methods section for validation and deeper review.
Citation
P Calabresi et al. (1992). Long-term synaptic depression in the striatum: physiological and pharmacological characterization. Journal of Neuroscience
Unilateral nigral injection of 6-hydroxydopamine • Protocol step
“LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine”
Prepare striatal slices • Protocol step
“slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine”
Set up extracellular and intracellular recordings • Protocol step
“The effect of tetanic activation of corticostriatal glutamatergic fibers was studied in striatal slices by utilizing extracellular and intracellular recording techniques”
Apply exogenous dopamine to restore LTD • Protocol step
“In DA-depleted slices, LTD could be restored by applying exogenous DA (30 microM) before the conditioning tetanus”
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