Article Figures & Data
Figures
- Figure 1.
Presynaptic activity modulates CB1-receptor-mediated inhibition of GABAergic transmission in the presence of exogenously applied cannabinoid agonists. A, In control ACSF (control), action potentials at 10 Hz in the presynaptic CCK+ basket cell (see supplemental Fig. 1, available at www.jneurosci.org as supplemental material) evoked IPSCs (eIPSCs) in the postsynaptic pyramidal cell (upper traces, presynaptic spikes; gray traces, eIPSCs, including failures; black traces, averaged eIPSCs without failures). As expected, these eIPSCs were abolished by the application of the CB1 receptor agonist 5 μm WIN (10 Hz). However, when the presynaptic firing was increased to 20 or 40 Hz in the same cell, the transmission reappeared, despite the continued presence of the agonist (WIN, 20 Hz; WIN, 40 Hz). B, C, Summary data showing the frequency-dependent changes in eIPSC amplitude (B) and failure rates (C) in control ACSF and in WIN. The data were obtained from responses elicited by ∼100 presynaptic action potentials in each cell in control ACSF and in WIN (note that this analysis actually underestimates the recovery in WIN, because it considers all responses, including those at beginning of the 100 action-potential-long trials when the eIPSCs appeared from the WIN-induced blockade of GABA release; see supplemental Fig. 2B, available at www.jneurosci.org as supplemental material). D, E, Summary data (with example traces as insets) illustrating that GABAergic transmission observed in WIN at 40 Hz firing is dependent on N-type Ca2+ channels. Nife, Nifedipine; ω-con, ω-conotoxin GVIA. The asterisks indicate significant differences (paired t test, p < 0.05). Error bars represent SEM.
- Figure 2.
Basket cell firing rates modulate CB1-mediated inhibition of GABA release induced by the endogenous mobilization of cannabinoids. A, Depolarization of the postsynaptic cell evoked strong DSI when the presynaptic firing was 10 Hz. However, the same depolarization evoked a significantly smaller and shorter-lasting DSI when the interneuron firing was 40 Hz. The plot shows summary data from n = 6 pairs (insets, example traces; the averaged eIPSCs include failures). B, C, Burst-like trains of 15 action potentials at 100 Hz were able to evoke eIPSCs during DSI that was complete (i.e., 100% failure rate) with 10 Hz firing. Twelve traces are superimposed in B. Summary data are shown in C from n = 4 pairs. D, Summary data of relative success rates (during vs preceding DSI) observed with trains of 15 action potentials either at 10 or 100 Hz, in n = 8 pairs. Errors bars represent SEM.
Additional Files
Supplemental data
Files in this Data Supplement:
- supplemental material - Supplementary Figure 1. Anatomical and immunocytochemical identification of the recorded presynaptic interneurons in CA1. A, Example of a visualized basket cell (camera lucida drawing, based on intracellular filling with biocytin), with the soma located in the stratum radiatum (Str. Rad.). Note the axonal arbor within or close to the pyramidal cell layer (Str. Pyr.; the initial segment is located to the right of the soma, and is indicated with a thick line; Str. Oriens: Stratum oriens). B, The immunochemical identification of the biocytin-filled interneuron shown in A revealed the presence of cholecystokinin (CCK), but the cell was immunonegative for parvalbumin.
- supplemental material - Supplementary Figure 2. Antagonism by AM251 of the WIN- and DSI-induced suppression of eIPSCs, and the course of the recovery from CB1 agonist-induced suppression of GABA-release. A, The CB1 antagonist AM251 (10 μM) reversed the blockade of eIPSCs by WIN55,212-2 (WIN; 5μM; presynaptic firing rate: 10Hz). B, Course of the recovery from the WIN-induced blockade of GABA-release (Control: n=11 pairs; WIN: n=9 pairs; bin size: 5 action potentials; �Normalized eIPSCs (%)� includes failures; presynaptic firing frequency: 40Hz). Note that the full recovery from WIN-inhibition took place in about 25 action potentials at 40Hz. C, The CB1 antagonist AM251 (10μM) abolished DSI (traces shown are from the same cell pair; n=4 pairs; presynaptic firing frequency: 10Hz).
