Endogenous cannabinoids trigger the depolarization-induced suppression of excitation in the lateral amygdala

Kodirov, Sodikdjon A.; Jasiewicz, Julia; Amirmahani, Parisa; Psyrakis, Dimitrios; Bonni, Kathrin; Wehrmeister, Michael; Lutz, Beat

doi:10.1101/lm.1663410

Cited by 47 publications

(56 citation statements)

References 38 publications

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“…Inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) are transiently suppressed after depolarization of postsynaptic neurons through retrograde endocannabinoid signaling; this phenomenon is known as DSI and DSE (23)(24)(25)(26). In the BLA, it has been reported that DSI and DSE as well as long-term depression at inhibitory synapses are induced by CB 1 activation (19,20,(27)(28)(29). In the present study, we compared induction profiles of DSI and DSE by recording from BA pyramidal neurons in acute slices (Fig.…”

Section: Dsi Is More Readily Induced and Saturated Than Dse In Ba Pyrmentioning

confidence: 97%

Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus

Yoshida

Uchigashima

Yamasaki

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

101

104

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2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of synaptic transmission in the brain. 2-AG is synthesized in activated postsynaptic neurons by sn-1-specific diacylglycerol lipase (DGL), binds to presynaptic cannabinoid CB 1 receptors, suppresses neurotransmitter release, and is degraded mainly by monoacylglycerol lipase (MGL). In the basolateral amygdala complex, it has been demonstrated that CB 1 is particularly enriched in axon terminals of cholecystokinin (CCK)-positive GABAergic interneurons, induces short-and long-term depression at inhibitory synapses, and is involved in extinction of fear memory. Here, we clarified a unique molecular convergence of DGLα, CB 1 , and MGL at specific inhibitory synapses in the basal nucleus (BA), but not lateral nucleus, of the basolateral amygdala. The synapses, termed invaginating synapses, consisted of conventional symmetrical contact and unique perisynaptic invagination of nerve terminals into perikarya. At invaginating synapses, DGLα was preferentially recruited to concave somatic membrane of postsynaptic pyramidal neurons, whereas invaginating presynaptic terminals highly expressed CB 1 , MGL, and CCK. No such molecular convergence was seen for flat perisomatic synapses made by parvalbumin-positive interneurons. On the other hand, DGLα and CB 1 were expressed weakly at axospinous excitatory synapses. Consistent with these morphological data, thresholds for DGLα-mediated depolarizationinduced retrograde suppression were much lower for inhibitory synapses than for excitatory synapses in BA pyramidal neurons. Moreover, depolarization-induced suppression was readily saturated for inhibition, but never for excitation. These findings suggest that perisomatic inhibition by invaginating synapses is a key target of 2-AGmediated control of the excitability of BA pyramidal neurons.retrograde signaling | metabotropic glutamate receptor | muscarinic acetylcholine receptor | depolarization-induced suppression of inhibition | depolarization-induced suppression of excitation M arijuana and other derivatives of the plant Cannabis sativa exert diverse neuropsychopharmacological actions, such as hallucination, euphoria, sedation, memory impairment, anxiolytic effect, appetite stimulation, motor deficit, and pain relief. These actions are mediated by Δ9-tetrahydrocannabinol (Δ9-THC), an active component of cannabis, through its binding to cannabinoid CB 1 receptors (1). CB 1 is particularly abundant in specific types of neurons, is selective to presynaptic elements, and induces shortand long-term forms of retrograde suppression of neurotransmitter release (1). In the brain, 2-arachidonoylglycerol (2-AG) is the major endogenous cannabinoid, synthesized in postsynaptic neurons by sn-1-specific diacylglycerol lipase (DGL) (2), and degraded mainly by monoacylglycerol lipase (MGL) (3, 4). 2-AG synthesis is facilitated when depolarization of postsynaptic neurons is combined with G q/11 -coupled receptor activation (1). Selective postsynaptic expression...

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Section: Dsi Is More Readily Induced and Saturated Than Dse In Ba Pyrmentioning

confidence: 97%

Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus

Yoshida

Uchigashima

Yamasaki

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

101

104

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“…We have encountered that the PPF at cortical inputs into the LA occurs less compared to other regions of the brain (Kodirov et al, 2009). A recent study demonstrates that the magnitude of PPF at these synapses decreases after a pairing paradigm from the ratio of ~2 to 1.5, at least one can estimate from representative traces (Fourcaudot et al, 2008).…”

Section: Molecular Substrate Of Ltpmentioning

confidence: 99%

“…They are pyramidal and interneurons, and both are prone to plasticity (Mahanty & Sah, 1998;Tully et al, 2007). These neurons are distinguished by means of various methods; however, their electrophysiological properties could be considered a main criterion (Kodirov et al, 2009). In recent years, the attempt to recognize both types of cells by usage of biological marker  green fluorescent protein (GFP)  are starting to emerge.…”

Section: Characteristics Of La and Bla Cells Involved In Plasticitymentioning

confidence: 99%

The Role of Norepinephrine in Amygdala Dependent Fear Learning and Memory

Kodirov¹

2012

The Amygdala - A Discrete Multitasking Manager

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“…2A). This postsynaptic depolarization causing a transient suppression of GABA or glutamate release is termed depolarization-induced suppression of inhibition (DSI) (Pitler and Alger, 1992) or excitation (DSE), respectively (Kodirov et al, 2010;Kreitzer and Regehr, 2001b). This method is used to measure retrograde eCB production and signalling, and has been shown to occur in core regions implicated in the stress response, including the hippocampus (Pitler and Alger, 1992), amygdala (Kodirov et al, 2010), prefrontal cortex (Yoshino et al, 2011) and hypothalamus (Wamsteeker et al, 2010).…”

Section: Ecbs and Stressmentioning

confidence: 99%

“…This postsynaptic depolarization causing a transient suppression of GABA or glutamate release is termed depolarization-induced suppression of inhibition (DSI) (Pitler and Alger, 1992) or excitation (DSE), respectively (Kodirov et al, 2010;Kreitzer and Regehr, 2001b). This method is used to measure retrograde eCB production and signalling, and has been shown to occur in core regions implicated in the stress response, including the hippocampus (Pitler and Alger, 1992), amygdala (Kodirov et al, 2010), prefrontal cortex (Yoshino et al, 2011 and hypothalamus (Wamsteeker et al, 2010).Interestingly, induction of DSI in one cell can inhibit nearby synapses as well ). Application of the group I mGluR agonist DHPG causes a comparable suppression of evoked inhibitory postsynaptic currents (eIPSCs), through enhanced production of eCBs, confirmed by occlusion with the CB1R agonist WIN55,212-2 (WIN) (Neu et al, 2007;Maejima et al, 2001).…”

mentioning

confidence: 99%

Neuromodulators, stress and plasticity: a role for endocannabinoid signalling

Senst

Bains

2014

Journal of Experimental Biology

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Any unanticipated threat to survival triggers an immediate sequence of events in the brain that culminate in a coordinated neural, endocrine and behavioural response. There is increasing evidence that stress itself modifies neural circuits. In other words, neural stress circuits learn from stress. This self-teaching is surprising as one might expect these essential circuits to be hard-wired. Our recent findings, however, indicate that repeated homotypic stress in rats causes functional changes in neural circuitry in the hypothalamus. In particular, we focus on signalling via endocannabinoids and describe plasticity in this system that impacts fast retrograde signalling at synapses on to the stress command neurons in the brain. Interestingly, this plasticity appears to be limited to early adolescence, hinting at unique modes of control of neural circuits by stress during different developmental stages. KEY WORDS: Hypothalamus, Neuromodulation, Neurobiology IntroductionIn all organisms, maintaining a stable internal environment and responding to external threats is vital for survival. This requires the ability to sense, transduce and respond effectively to real and perceived stress. In mammals, multiple brain nuclei are activated in response to both physiological and psychological challenges. When faced with a challenge to internal homeostasis or an unanticipated, direct threat to survival, this 'stress circuitry' rapidly sets in motion a cascade of neural, neuroendocrine and behavioural responses. Mounting an appropriate physiological response to such challenges requires that the brain interprets, learns from and then remembers the appropriate stimuli. This series of tasks is accomplished by groups of interconnected neural networks that incorporate information from sensory systems, process this information in higher brain centres then engage downstream effectors to coordinate generalized behavioural and physiological adaptation to change. In the short-term, these adaptations are beneficial as they allow the organism to respond to the threat. They also promote learning, which results in more refined responses to subsequent challenges. When launched inappropriately, however -for example, in the absence of stress -they can have deleterious effects on mental and physical health (McEwen and Gianaros, 2011;Stetler and Miller, 2011).At the organismal level, stress is a complicated response to study as there are a myriad of genetic, environmental and social contributions that influence how the body is designed to respond to challenges (Russo et al., 2012). In addition, the network of mediators that influence neural and neuroendocrine responses function in a non-linear fashion (McEwen, 2006). In an effort to better understand how the neuroendocrine response to stress is initiated and modified, we have focused exclusively on synapses that provide direct input to parvocellular neurosecretory cells (PNCs) in the paraventricular nucleus of the hypothalamus (PVN). These cells are the apex of the hypothalamic-pituitary-...

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Endogenous cannabinoids trigger the depolarization-induced suppression of excitation in the lateral amygdala

Cited by 47 publications

References 38 publications

Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus

Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus

The Role of Norepinephrine in Amygdala Dependent Fear Learning and Memory

Neuromodulators, stress and plasticity: a role for endocannabinoid signalling

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