Excitation of medium spiny neurons by ‘inhibitory’ ultrapotent chemogenetics via shifts in chloride reversal potential
- Department of Molecular Physiology and Biophysics, University of Iowa, United States
- Biological and Biomedical Neuroscience Program, University of North Carolina, United States
- National Institute on Drug Abuse, United States
- Department of Psychiatry, School of Medicine, University of Pittsburgh, United States
Figures
Figure 1
In vivo activation of PSAM4-GlyR enhances c-fos expression in D1-MSNs.
(A) Left, cartoon of viral injection site in the ventral striatum. Right, representative confocal images of Cre-dependent PSAM4-GlyR expression (eGFP) in Cre-expressing D1-MSNs (tdTomato). (B) …
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Figure 1—source data 1
PSAM4-GlyR enhances c-fos expression in D1-MSNs in-vivo (source data).
- https://cdn.elifesciences.org/articles/64241/elife-64241-fig1-data1-v1.xlsx
Figure 2
Activation of PSAM4-GlyR in D1-MSNs produces an inward current.
(A) Representative traces of whole-cell voltage-clamp recordings (Vhold −88 mV) demonstrate no effect of uPSEM792 (10 or 50 nM) in control neurons. In PSAM4-GlyR+ neurons, 10 or 50 nM uPSEM792 …
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Figure 2—source data 1
of PSAM4-GlyR depolarizes D1-MSNs (source data).
- https://cdn.elifesciences.org/articles/64241/elife-64241-fig2-data1-v1.xlsx
Figure 3
Activation of PSAM4-GlyR depolarizes D1-MSNs and does not inhibit firing.
(A) In PSAM4-GlyR+ neurons, activation of PSAM4-GlyR with uPSEM792 (10 and 50 nM) significantly depolarized the membrane potential (Vm) compared to control (non-PSAM4-GlyR) neurons, measured in …
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Figure 3—source data 1
PSAM4-GlyR does not inhibit firing of D1-MSNs (source data).
- https://cdn.elifesciences.org/articles/64241/elife-64241-fig3-data1-v1.xlsx
Figure 4
In cell-attached configuration, activation of PSAM4-GlyR triggers firing of D1-MSNs when the membrane is depolarized to subthreshold potentials.
(A) Representative traces of cell-attached recordings from a control (gray) or PSAM4-GlyR+ neuron in standard aCSF (4.5 mM [K+]). Action currents were evoked following uPSEM792 by applying a high …
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Figure 4—source data 1
PSAM4-GlyR induces D1-MSN firing in cell-attached recordings (source data).
- https://cdn.elifesciences.org/articles/64241/elife-64241-fig4-data1-v1.xlsx
Figure 5
Current–voltage relationship of PSAM4-GlyR current shows rightward shift in reversal potential and transient or small outward currents at depolarized potentials.
(A) Current was recorded in response to voltage steps (1 s, −118 to −28 mV, 10 mV) from Vhold −88 mV in aCSF and after application of uPSEM792 (50 or 100 nM). uPSEM792-induced current was isolated …
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Figure 5—source data 1
Current-voltage relationship of PSAM4-GlyR current (source data).
- https://cdn.elifesciences.org/articles/64241/elife-64241-fig5-data1-v1.xlsx
Figure 6
PSAM4-GlyR activation in D1-MSNs reduces GABAergic synaptic inhibition.
(A) Representative traces of GABA-A receptor-mediated synaptic currents in a PSAM4-GlyR+ neuron in aCSF, evoked during voltage steps from Vhold −88 mV (voltage steps: 1 s, −118 to −28 mV, 10 mV; …
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Figure 6—source data 1
Reduced GABAergic synaptic inhibition (source data).
- https://cdn.elifesciences.org/articles/64241/elife-64241-fig6-data1-v1.xlsx
