ECS (2019 Cannabinoid & Plasticity PhD Review Concepts)

[Intro] (spoken, low, slightly reverbed) Yeah... Dr. K-dope. The system was already in your skull before the plant ever crossed the border. Let's talk about it. [Verse 1] CB1 — most expressed receptor in the dome More than mGlu, that's the throne where the lipids roam Anandamide, named for bliss in the ancient tongue Two-AG riding shotgun where the synapse hung Retrograde signal, postsynaptic talking back Telling pre, "ease up off the glutamate attack" DSI, DSE, milliseconds to a minute Short-term plasticity, the eCB lives in it But that's surface level — pun fully intended 'Cause the story of the cannabinoid ain't where it ended Hebb said neurons that fire wire — that's the law But Turrigiano said the brain need a failsafe draw Homeostatic scaling, the dialectic in the cortex Learn but don't explode, that's the balancing the brain forced And right between those forces, who you think the broker? Endocannabinoid system, dealing every poker [Pre-Chorus] Same lipid, two timescales, the brain stay tuning Hebb on the left, homeostasis on the right Anandamide and 2-AG in the room And the system in your skull deciding what's right [Hook] It's the E-C-S — every synapse got a switch (Switch it up, switch it up) Plasticity, homeostasis, that's the bridge (Bridge it up, bridge it up) CB1, CB2, mitochondria too (All the way through, all the way through) Science is dope, and the dope is in YOU (In YOU, in YOU) [Verse 2] Silva-Cruz, twenty-seventeen, hippocampal slice Weak theta bursts, strong theta bursts, rolled the dice CB1 antagonist — AM251 in the bath Weak LTP got LOUDER when they blocked the path Strong LTP got quieter — peep the math The receptor act a high-pass, filtering wrath It's a bouncer at the club of long-term memory "Weak signal? Get gone. Strong signal? Come see." And the AEA push opposite the 2-AG Two endogenous lipids, two different keys Park studied LHb — habenula, lateral Low-frequency stim induced an LTD spectacle But block the CB1, that depression don't manifest The mood circuit modulated by the ligand in the chest Same system that handle whether memories endure Touching circuits that decide if you depressed or pure [Pre-Chorus] Same lipid, two timescales, the brain stay tuning Hebb on the left, homeostasis on the right Anandamide and 2-AG in the room And the system in your skull deciding what's right [Hook] It's the E-C-S — every synapse got a switch (Switch it up, switch it up) Plasticity, homeostasis, that's the bridge (Bridge it up, bridge it up) CB1, CB2, mitochondria too (All the way through, all the way through) Science is dope, and the dope is in YOU (In YOU, in YOU) [Bridge] (slightly slower, more sparse, vocal upfront) Now Hébert-Chatelain pulled the curtain back further CB1 ain't just on the membrane, partner On the mitochondria — call it mtCB1 Power plant of the cell, where the ATP run Activate it, complex one slow down the chain Less ATP made, less oxygen drained Mitochondria freeze, can't travel to the spike Calcium goes off, the homeostasis ain't right DN22 mutant mouse — no mtCB1 Give it cannabinoid agonist, memory don't run The forgetting wasn't synaptic the whole time It was metabolic — y'all rewriting the textbook lines Song, Turrigiano, scaling at the excitatory site JZL184 block the MAGL, mEPSC frequency dropped overnight From the membrane to the matrix, from a second to a day Same family of lipids, same conductor in the play [Hook] It's the E-C-S — every synapse got a switch (Switch it up, switch it up) Plasticity, homeostasis, that's the bridge (Bridge it up, bridge it up) CB1, CB2, mitochondria too (All the way through, all the way through) Science is dope, and the dope is in YOU (In YOU, in YOU) [Outro] (spoken, fading) The system was already in you. Anandamide. Bliss molecule. Schizophrenia, ADHD, anxiety, addiction — all the disorders we don't fully understand yet touching the same dial. That's the dialectic of Hebb and homeostasis. And we're just getting started. Peer-reviewed. Dr. K-dope. Out.