{
 "version": "1.0.0",
 "about": "Neurotransmitters for the Neurotransmitters tab. levels: region id -> H / M / L = how much of this transmitter's signalling (release sites, receptors or fibre density) the region has, relative to other regions, from the reviews in refs (qualitative). A level on a parent region applies to its sub-regions unless they have their own. sources = regions where the transmitter's neurons sit. scope: general = used throughout the brain; diffuse = made in a few small nuclei, released widely; local = mainly in a few regions.",
 "levels": {
  "H": "High",
  "M": "Medium",
  "L": "Low"
 },
 "transmitters": [
  {
   "id": "glutamate",
   "title": "Glutamate",
   "short": "Glu",
   "color": "#e53935",
   "kind": "Excitatory",
   "group": "Fast signals",
   "scope": "general",
   "about": "The brain's main 'go' signal. Most neurons in the cortex, hippocampus, thalamus and cerebellum release glutamate, and most synapses in the brain use it. It makes the next neuron more likely to fire, and it drives learning (long-term potentiation).",
   "does": [
    "Fast excitatory signalling",
    "Learning and memory (LTP)",
    "Carrying senses to the cortex"
   ],
   "sources": [],
   "made": "Made by most neurons themselves; recycled through astrocytes (the glutamate–glutamine cycle).",
   "energy": "Clearing glutamate after each signal and restoring the ion gradients it opens is the largest energy cost of brain signalling. When energy runs short, glutamate uptake stalls and can even run backwards, so glutamate builds up and over-excites neurons (excitotoxicity).",
   "levels": {
    "cerebrum": "H",
    "hippocampus": "H",
    "cerebellum": "H",
    "thalamus": "H",
    "amygdala": "M",
    "hypothalamus": "M",
    "brainstem": "M",
    "olfactory_bulb": "H"
   },
   "refs": [
    "zhou2014",
    "attwell2001",
    "rossi2000"
   ]
  },
  {
   "id": "gaba",
   "title": "GABA",
   "short": "GABA",
   "color": "#1e88e5",
   "kind": "Inhibitory",
   "group": "Fast signals",
   "scope": "general",
   "about": "The brain's main 'brake'. GABA makes the next neuron less likely to fire. About a fifth of cortical neurons are GABA interneurons that shape timing and rhythms; Purkinje cells, the output of the cerebellum, all use GABA.",
   "does": [
    "Fast inhibition",
    "Timing and brain rhythms",
    "Calming excitation (anti-seizure)"
   ],
   "sources": [],
   "made": "Made from glutamate inside inhibitory neurons (by the enzyme GAD).",
   "energy": "Fast-spiking GABA interneurons are among the most energy-hungry cells in the brain. When energy is short, inhibition and the fast rhythms they pace fail early.",
   "levels": {
    "cerebellum": "H",
    "hypothalamus": "H",
    "tegmentum": "H",
    "amygdala": "H",
    "septal": "H",
    "thalamus": "M",
    "cerebrum": "M",
    "hippocampus": "M",
    "olfactory_bulb": "H",
    "pons": "L",
    "medulla": "M",
    "caudate": "H",
    "putamen": "H",
    "globus_pallidus": "H",
    "nucleus_accumbens": "H",
    "substantia_nigra": "H"
   },
   "refs": [
    "petroff2002",
    "kann2016"
   ]
  },
  {
   "id": "glycine",
   "title": "Glycine",
   "short": "Gly",
   "color": "#5e35b1",
   "kind": "Inhibitory",
   "group": "Fast signals",
   "scope": "local",
   "about": "An inhibitory transmitter used mostly in the brainstem and spinal cord, where it controls reflexes, muscle tone and the breathing rhythm. In the rest of the brain glycine mainly acts as a helper that NMDA-type glutamate receptors need.",
   "does": [
    "Inhibition in brainstem and spinal cord",
    "Reflexes and muscle tone",
    "Breathing rhythm"
   ],
   "sources": [
    "medulla",
    "pons"
   ],
   "made": "Made by inhibitory neurons in the medulla, pons and spinal cord.",
   "energy": null,
   "levels": {
    "medulla": "H",
    "pons": "H",
    "midbrain": "L",
    "cerebellum": "L"
   },
   "refs": [
    "legendre2001"
   ]
  },
  {
   "id": "acetylcholine",
   "title": "Acetylcholine",
   "short": "ACh",
   "color": "#00897b",
   "kind": "Modulator",
   "group": "Modulators",
   "scope": "diffuse",
   "about": "Made by a few clusters of neurons in the basal forebrain (next to the septal area) and the brainstem, whose long axons reach the hippocampus, cortex and thalamus. It sharpens attention and helps lay down new memories. (It is also the transmitter that makes muscles contract.)",
   "does": [
    "Attention",
    "Forming new memories",
    "Waking and REM sleep"
   ],
   "sources": [
    "septal",
    "tegmentum",
    "pons"
   ],
   "made": "Basal forebrain (medial septum, nucleus basalis) and the pedunculopontine / laterodorsal tegmental nuclei of the brainstem.",
   "energy": "Basal-forebrain acetylcholine neurons are lost early in Alzheimer's disease, a disease in which brain glucose use also falls.",
   "levels": {
    "hippocampus": "H",
    "thalamus": "H",
    "amygdala": "H",
    "cerebrum": "M",
    "cingulate": "M",
    "olfactory_bulb": "M",
    "septal": "M",
    "tegmentum": "M",
    "pons": "M",
    "caudate": "H",
    "putamen": "H"
   },
   "refs": [
    "woolf1991",
    "cunnane2020"
   ]
  },
  {
   "id": "dopamine",
   "title": "Dopamine",
   "short": "DA",
   "color": "#fb8c00",
   "kind": "Modulator",
   "group": "Modulators",
   "scope": "diffuse",
   "about": "Made by two small groups of neurons in the midbrain (substantia nigra and ventral tegmental area). Their axons reach the striatum (movement and habits), the prefrontal cortex and limbic areas (motivation, 'wanting'). A third group in the hypothalamus controls the pituitary (prolactin).",
   "does": [
    "Motivation and wanting",
    "Learning from reward",
    "Starting movements"
   ],
   "sources": [
    "substantia_nigra",
    "tegmentum",
    "hypothalamus"
   ],
   "made": "Substantia nigra and ventral tegmental area (midbrain); arcuate nucleus of the hypothalamus.",
   "energy": "Substantia nigra dopamine neurons fire non-stop like pacemakers and have huge axon trees, so they need a lot of energy - one reason they are the first to die in Parkinson's disease.",
   "levels": {
    "tegmentum": "H",
    "prefrontal": "M",
    "cingulate_ant": "M",
    "amygdala": "M",
    "olfactory_bulb": "M",
    "pituitary": "M",
    "hypothalamus": "M",
    "hippocampus": "L",
    "cerebrum": "L",
    "caudate": "H",
    "putamen": "H",
    "nucleus_accumbens": "H",
    "substantia_nigra": "H"
   },
   "note": "The highest levels are in the striatum (basal ganglia), which lies off the midline and is not on this drawing.",
   "refs": [
    "bjorklund2007",
    "pacelli2015"
   ]
  },
  {
   "id": "norepinephrine",
   "title": "Norepinephrine",
   "short": "NE",
   "color": "#8e24aa",
   "kind": "Modulator",
   "group": "Modulators",
   "scope": "diffuse",
   "about": "Also called noradrenaline. Almost all of it in the brain comes from the locus coeruleus, a tiny nucleus in the pons with only a few tens of thousands of neurons, whose axons branch to nearly every region. It raises alertness and focus, and drives the stress response.",
   "does": [
    "Alertness and arousal",
    "Focus under stress",
    "Fight-or-flight"
   ],
   "sources": [
    "locus_coeruleus",
    "pons",
    "medulla"
   ],
   "made": "Locus coeruleus (pons); smaller groups in the medulla.",
   "energy": "Norepinephrine tells astrocytes to break down their glycogen and release fuel for neurons, and it helps control blood flow in the brain.",
   "levels": {
    "hypothalamus": "H",
    "thalamus": "H",
    "amygdala": "H",
    "pons": "H",
    "hippocampus": "M",
    "cerebrum": "M",
    "cerebellum": "M",
    "medulla": "M",
    "midbrain": "M",
    "locus_coeruleus": "H"
   },
   "refs": [
    "schwarz2015",
    "ohm1997",
    "brown2007"
   ]
  },
  {
   "id": "serotonin",
   "title": "Serotonin",
   "short": "5-HT",
   "color": "#d81b60",
   "kind": "Modulator",
   "group": "Modulators",
   "scope": "diffuse",
   "about": "Made by the raphe nuclei along the midline of the brainstem and sent to almost the whole brain. It tunes mood, anxiety, appetite, sleep and impulse control. (About 90 % of the body's serotonin is in the gut, not the brain.)",
   "does": [
    "Mood and anxiety",
    "Sleep and appetite",
    "Impulse control"
   ],
   "sources": [
    "midbrain",
    "pons",
    "medulla"
   ],
   "made": "Raphe nuclei of the midbrain, pons and medulla.",
   "energy": null,
   "levels": {
    "hypothalamus": "H",
    "amygdala": "H",
    "septal": "M",
    "hippocampus": "M",
    "cerebrum": "M",
    "thalamus": "M",
    "midbrain": "H",
    "pons": "M",
    "medulla": "M",
    "cerebellum": "L"
   },
   "refs": [
    "hornung2003"
   ]
  },
  {
   "id": "histamine",
   "title": "Histamine",
   "short": "HA",
   "color": "#6d4c41",
   "kind": "Modulator",
   "group": "Modulators",
   "scope": "diffuse",
   "about": "Made by one small cluster, the tuberomammillary nucleus at the back of the hypothalamus, whose axons reach the whole brain. Brain histamine keeps you awake - which is why older antihistamines that enter the brain make people drowsy.",
   "does": [
    "Wakefulness",
    "Appetite",
    "Attention"
   ],
   "sources": [
    "hypothalamus"
   ],
   "made": "Tuberomammillary nucleus of the posterior hypothalamus.",
   "energy": null,
   "levels": {
    "hypothalamus": "H",
    "cerebrum": "M",
    "thalamus": "M",
    "amygdala": "M",
    "hippocampus": "M",
    "tegmentum": "M"
   },
   "refs": [
    "haas2003"
   ]
  },
  {
   "id": "adenosine",
   "title": "Adenosine",
   "short": "Ado",
   "color": "#546e7a",
   "kind": "Modulator",
   "group": "Modulators",
   "scope": "general",
   "about": "Not stored in vesicles like the others: it forms outside cells from ATP that has been used up, and acts on A1 receptors (dense in the hippocampus, cortex, thalamus and cerebellum) to slow neurons down. It builds up the longer you are awake and helps make you sleepy; caffeine works by blocking it.",
   "does": [
    "Sleep pressure",
    "Slowing down overactive neurons",
    "Protection when energy is low"
   ],
   "sources": [],
   "made": "Made everywhere, from the breakdown of ATP.",
   "energy": "Adenosine is the brain's energy gauge. When ATP is used faster than it is made, adenosine rises and turns neurons and synapses down - a built-in brake that saves energy.",
   "levels": {
    "hippocampus": "H",
    "cerebrum": "H",
    "thalamus": "H",
    "cerebellum": "H",
    "hypothalamus": "M",
    "amygdala": "M",
    "brainstem": "L"
   },
   "refs": [
    "dunwiddie2001",
    "porkka1997"
   ]
  },
  {
   "id": "orexin",
   "title": "Orexin (hypocretin)",
   "short": "Ox",
   "color": "#c0ca33",
   "kind": "Neuropeptide",
   "group": "Neuropeptides",
   "scope": "diffuse",
   "about": "A small peptide made by only about 70,000 neurons in the lateral hypothalamus. They switch on the brain's arousal centres (locus coeruleus, raphe, histamine neurons) and keep you awake; losing them causes narcolepsy.",
   "does": [
    "Staying awake",
    "Food seeking",
    "Linking energy state to arousal"
   ],
   "sources": [
    "hypothalamus"
   ],
   "made": "Lateral hypothalamus.",
   "energy": "Orexin neurons are energy sensors: rising glucose switches them off and falling glucose lets them fire, so hunger makes you more alert and food-seeking.",
   "levels": {
    "hypothalamus": "H",
    "pons": "H",
    "midbrain": "H",
    "tegmentum": "H",
    "thalamus": "M",
    "cerebrum": "M",
    "septal": "M"
   },
   "refs": [
    "sakurai2007",
    "thannickal2000",
    "burdakov2005"
   ]
  },
  {
   "id": "opioids",
   "title": "Endorphins & enkephalins",
   "short": "Opi",
   "color": "#f4511e",
   "kind": "Neuropeptide",
   "group": "Neuropeptides",
   "scope": "diffuse",
   "about": "The brain's own opioids. Beta-endorphin is made in the hypothalamus; enkephalins and dynorphins are made by neurons in many regions. They damp pain (especially in the midbrain's periaqueductal grey) and give the 'liking' part of reward.",
   "does": [
    "Pain relief",
    "Pleasure and reward",
    "Stress relief"
   ],
   "sources": [
    "hypothalamus"
   ],
   "made": "Beta-endorphin: arcuate nucleus of the hypothalamus; enkephalin and dynorphin: many local neurons.",
   "energy": null,
   "levels": {
    "midbrain": "H",
    "hypothalamus": "H",
    "amygdala": "H",
    "tegmentum": "H",
    "thalamus": "M",
    "cingulate_ant": "M",
    "septal": "M",
    "medulla": "M"
   },
   "refs": [
    "lemerrer2009"
   ]
  },
  {
   "id": "oxytocin",
   "title": "Oxytocin & vasopressin",
   "short": "OT",
   "color": "#ec407a",
   "kind": "Neuropeptide",
   "group": "Neuropeptides",
   "scope": "local",
   "about": "Two closely related peptides made by large neurons in the hypothalamus. Most are carried down to the posterior pituitary and released into the blood (oxytocin: birth and breast-feeding; vasopressin: water balance). Smaller amounts act inside the brain on bonding, trust and social memory.",
   "does": [
    "Social bonding",
    "Birth and breast-feeding",
    "Water balance (vasopressin)"
   ],
   "sources": [
    "hypothalamus"
   ],
   "made": "Paraventricular and supraoptic nuclei of the hypothalamus.",
   "energy": null,
   "levels": {
    "hypothalamus": "H",
    "pituitary": "H",
    "amygdala": "M",
    "septal": "M",
    "hippocampus": "L",
    "medulla": "L"
   },
   "refs": [
    "gimpl2001"
   ]
  }
 ]
}