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. 2012 Jun 20;32(25):8475-9.
doi: 10.1523/JNEUROSCI.5333-11.2012.

Cannabinoid receptor-mediated regulation of neuronal activity and signaling in glomeruli of the main olfactory bulb

Ze-Jun Wang  1 , Liqin Sun, Thomas Heinbockel
Affiliations

Cannabinoid receptor-mediated regulation of neuronal activity and signaling in glomeruli of the main olfactory bulb

Ze-Jun Wang et al. J Neurosci. .

Abstract

Cannabinoid receptors (CB1Rs) are present in glomeruli of the main olfactory bulb. The functions of CB1Rs and their endogenous activators, endocannabinoids, for glomerular signaling are unknown. Glomeruli contain at least three types of neurons: periglomerular (PG), external tufted (ET), and short-axon (SA) cells. PG cells form inhibitory GABAergic dendrodendritic synapses with ET cells. ET cells form excitatory glutamatergic dendrodendritic synapses with PG and SA cells. In mouse brain slices, we used whole-cell patch-clamp recordings to study the role of CB1Rs in regulating PG and ET cells. Cannabinoids displayed strong, direct inhibitory effects on PG cells and weak effects on ET cells. Single pulses or a train of pulses of depolarizing current injected into an ET cell evoked suppression of IPSCs. This suggests retrograde endocannabinoid signaling, namely, depolarization-induced suppression of inhibition (DSI) in ET cells. Our results support the hypothesis that burst firing of ET cells triggers the release of endocannabinoids which in turn directly inhibit PG cells and reduce GABA release from PG cells. This, in turn, can result in a transient reduction of PG cell inhibitory input to ET cells.

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Figures

Figure 1.
Figure 1.
CB1R regulated the activity of periglomerular cells. A, B, Original recordings illustrate that CB1R agonist WIN reduced the firing rate of an sPG cell. CB1R antagonist AM251 increased spiking of an sPG cell. Recordings for WIN and AM251 are from the same sPG cell. C, Anandamide reduced firing and hyperpolarized membrane potential in an sPG cell. D, Summary of cannabinoid effects on sPG cell activity in absence and presence of synaptic blockers. E, Original recording illustrates depolarization of an nPG cell following bath application of AM251. sEPSPs were abolished following bath application of synaptic blockers (syn. blo.).
Figure 2.
Figure 2.
CB1R modified the activity of and synaptic transmission to ET cells. A(1), Extracellular recording from an ET cell in cell-attached voltage-clamp mode to initially identify ET cells by their burst firing pattern. A(2), A(3), The burst firing pattern of an ET cell recorded in absence and presence of CB1R antagonist AM251 in whole-cell current-clamp mode. The burst firing pattern of A(2) is shown at higher time resolution in A(4). B, AM251 increased the burst firing rate of an ET cell in the presence of synaptic blockers (10 μm CNQX + 50 μm d-AP5 and 5 μm gabazine). C, Group data illustrating the role of CB1R for burst firing of ET cells in absence and presence of synaptic blockers. Asterisks indicate significance level (*p < 0.05). D, AM251 induced an increase of sIPSCs in an ET cell in the presence of CNQX + d-AP5 with low-Cl−-based pipette solution. Holding potential is at 0 mV. IPSCs appeared as upward deflections. E, AM251 induced an increase of sIPSCs in ET cell in the presence of CNQX + d-AP5 with high-Cl−-based pipette solution. Holding potential was at −60 mV. sIPSCs appeared as downward deflections.
Figure 3.
Figure 3.
DSI in olfactory glomeruli. A, A depolarizing voltage step evoked DSI in a representative ET cell. High Cl−-based pipette solution was used for recording sIPSCs. Depolarization was achieved by stepping from −60 mV holding potential to 0 mV for 5 s. B, In the presence of CNQX and 5-AP, a train of 20 voltage steps to 0 mV (0.75 Hz; step duration: 667 ms) transiently reduced sIPSCs in an ET cell. Holding potential was −60 mV. C, In the presence of AM251, no sIPSC suppression was observed. D, A train of 20 voltage steps to −30 mV (2 Hz; step duration: 250 ms) transiently reduced sIPSCs in an ET cell (in CNQX and AP5). E, Normalized sIPSCs area illustrating the magnitude and time course of DSI elicited by a 5 s depolarizing pulse (n = 7). The averaged values between 0 and 5 s after the end of the voltage step were significantly different from the baseline (ANOVA and Bonferroni post hoc analysis, p < 0.05). F, Normalized sIPSC area illustrating the magnitude and time course of DSI elicited by a train of depolarizations to 0 mV (n = 12) in control and in the presence of AM251 (n = 10). In control conditions, the averaged values between 0 and 25 s after the end of the train of voltage steps were significantly different from the baseline (ANOVA and Bonferroni post hoc analysis, p < 0.05).
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