Functional Significance of Cannabinoid-Mediated, Depolarization-Induced Suppression of Inhibition (DSI) in the Hippocampus

Abstract

. Functional significance of cannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) in the hippocampus. J Neurophysiol 90: 55-64, 2003. First published March 20, 2003 10.1152/jn.01161.2002. A number of recent studies have demonstrated that a well-known form of short-term plasticity at hippocampal GABAergic synapses, called depolarization-induced suppression of inhibition (DSI), is in fact mediated by the retrograde actions of endocannabinoids released in response to depolarization of the postsynaptic cells. These studies suggest that endogenous cannabinoids may play an important role in regulating inhibitory tone in the mammalian CNS. Despite the widespread interest and potential physiological importance of DSI, many questions regarding the physiological relevance of DSI remain. To that end, this study set out to define the specific limiting conditions that could elicit DSI at GABAergic synapses in CA1 hippocampal pyramidal neurons and to determine if DSI could be elicited with pulse trains that mimic hippocampal cell-firing patterns that occur in vivo. Whole cell recordings from hippocampal neurons under voltage-clamp configuration were made in rat hippocampal slices. Spontaneous and evoked ␥-aminobutyric acid-A (GABA A ) receptor-mediated inhibitory postsynaptic currents (sIPSCs and eIPSCs, respectively) were recorded prior to and following depolarization of CA1 hippocampal pyramidal cells. Depolarizing voltage pulses were shaped to evoke currents in QX-314-treated cells similar to those accompanying single spontaneous voltage-clamped action potentials recorded from the soma. Attempts were made to elicit DSI with trains of these pulses that mimicked hippocampal cell firing patterns in vivo, for instance, when animals traverse place fields or are performing a short-term memory task. DSI could not be elicited by such pulse trains or by a number of other combinations of behaviorally specific firing parameters. The minimum duration of depolarization necessary to elicit DSI in hippocampal neurons determined by paired-pulse manipulation was 50 -75 ms at a critical interval of 20 -30 ms between pulse pairs. Under the conditions tested, the normal firing patterns of hippocampal neurons that occur in vivo do not appear to elicit DSI. We investigated DSI from two different perspectives: first, as to whether this process could be initiated in vitro by normal patterns of action potentials recorded from animals performing hippocampal-dependent behavioral tasks. This is important because it addresses the functional significance of DSI and associated endocannabinoids that are involved, since it appears that hippocampal neurons need to be significantly depolarized to release endocannabinoids (Lenz and Alger 1999;Wilson and Nicoll 2002). The second purpose was to define precisely the range of frequencies and minimum duration of depolarizing pulses required to elicit DSI in hippocampal pyramidal neurons in vitro. Both objectives were directed at determining whether release of endocannabinoids is possible ...

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

“…It must be mentioned, nonetheless, that a more recent paper, in which experiments very similar to those of Pitler & Alger, 1992 were performed, challenges this view (Hampson et al, 2003). We have noticed two main differences between these reports, although we cannot say if they can explain these contradictory results: the age of the animals used (1-week-old rats in Hampson et al, 2003 andadult rats in Pitler &Alger, 1992) …”

“…We have noticed two main differences between these reports, although we cannot say if they can explain these contradictory results: the age of the animals used (1-week-old rats in Hampson et al, 2003 andadult rats in Pitler &Alger, 1992) …”

The molecular logic of endocannabinoid signalling

“…Although this idea is still questioned 110 , various results link DSI to the regulation of hippocampal GAMMA OSCILLATIONS 77 . These network oscillations are coordinated by CB 1 -positive GABA interneurons and are influenced by cannabinoid agonists, raising the possibility that an endocannabinoid substance might modulate their expression 111 and be involved in the organization of hippocampal cell assemblies 112 .…”

Prefrontal Cortex Stimulation Induces 2-Arachidonoyl-Glycerol-Mediated Suppression of Excitation in Dopamine Neurons

“…Thus far, the importance of an endocannabinoid retrograde signal occurring within the range of physiologically in vivo firing patterns has been questioned because no supportive evidence subsists in vivo (Hampson et al, 2003). Therefore, in an attempt to investigate whether this endocannabinoid-dependent suppression of excitation is a physiologically relevant phenomenon in vivo, we studied the responses of VTA DA neurons to electrical stimulation of the medial PFC.…”

“…Therefore, one of the most important challenges is to determine possible physiological modes of DSE-DSI induction. Hence, studies aimed at establishing the physiological patterns of synaptic activity required to induce endocannabinoid release have just started (Brown et al, 2003;Hampson et al, 2003;Fortin et al, 2004;Galante and Diana, 2004). Dopamine (DA) neurons of the ventral tegmental area (VTA) play a central role in motivation, reward-related behaviors, and cognition (Schultz, 2002).…”