Endogenous cannabinoid molecules are prime examples of principal modulators of synaptic activity. Our previous work (as part of Tamás Freund’s laboratory) contributed to the discovery that the lipid-derived endocannabinoid known as 2-arachidonoyl-glycerol (2-AG), and its receptor, the CB₁ cannabinoid receptor serve a key physiological role in the regulation of neurotransmitter release as part of a retrograde messenger system (see for example: Katona et al. 1999, Journal of Neuroscience, 19: 4544-4558; Katona et al., 2006, Journal of Neuroscience, 24:5268-5237). We proposed a model describing how this peculiar molecular machinery may operate as a synaptic circuit breaker at excitatory glutamatergic synapses, to protect against excessive presynaptic activity (Katona and Freund, 2008, Nature Medicine, 14:923-930). The physiological importance of this synaptic circuit breaker is demonstrated in the phenomenon of stress-induced analgesia in the spinal cord for which the molecular players of the 2-AG messenger system are indispensable (Nyilas et al., 2009, European Journal of Neuroscience, 29:1964-1978). Moreover, this signaling pathway is robustly impaired in the hippocampal formation of epileptic patients, which may exacerbate the progression of epileptic activity and neuronal damage, thereby highlighting the pathophysiological significance of synaptic endocannabinoid signaling (Ludányi et al., 2008, Journal of Neuroscience, 28:2976-2990).

  Despite its pivotal importance, key aspects of the endocannabinoid signaling system remain elusive and in some cases even controversial. Furthermore, recent advances have revealed the presence of an unexpected number and diversity of endocannabinoid-related bioactive lipid molecules, as well as their potential metabolic enzymes and receptors in the brain. In accordance, we have provided evidence that NAPE-PLD, a crucial biosynthetic enzyme of N-acylethanolamines (NAEs), the family of lipids containing the archetypical endocannabinoid molecule anandamide, is positioned in axon terminals. This presynaptic accumulation of NAPE-PLD indicates that NAEs may also be synaptic messengers, but does not support the notion that these lipid mediators act as retrograde messengers (Nyilas et al., 2008, Journal of Neuroscience, 28:1058-1063).

  Taken together, it is conceivable that these various molecular players were evolved tofulfill specific requirements of neuronal activity and may regulate distinct aspects of synaptic transmission. Therefore, research activity in our laboratory is focusing on the characterization of these novel lipid pathways and we aim to reveal their synapse-specific functions by using a combination of experimental approaches including molecular and cell biology, neuroanatomy and neurophysiology. Our research is currently supported by the Starting Independent Research Grant from the European Research Council and by the OTKA-Norwegian Financial Mechanisms.

  As a relatively newborn international research group, we would also welcome enquiries from motivated young students and colleagues with a shared research interest, who would like to join us in our endeavor.