COGNITIVE SCIENCE 17 The Chemical Brain
Transcript of COGNITIVE SCIENCE 17 The Chemical Brain
COGNITIVE SCIENCE 17
The Chemical Brain
Part 2
Matt Schalles, Rev.
Classes of Neurotransmitters
● Amino Acids fast +/- (sensory/motor)● Glutamate and GABA cortex → cortex
● Biogenic Amines slow +/-/modulatory● Acetylcholine, Dopamine, midbrain → cortex● Norepinephrine, Serotonin
● Neuropeptides ● Endorphins
● Others● Lipids, gases
Glutamate
● Principal excitatory NT● Biosynthesized as byproduct of cell metabolism (Krebs
cycle)● Removed by reuptake● 4 receptor types
● NMDA● AMPAa● Kainate● AMPAb Metabotropic
Ionotropic
NMDA Binding Sites
● 4 outside cell● Glutamate● Glycine
– Obligatory co-agonist– Inhibitory NT at its “own” receptor
● Zinc (inverse agonist)● Polyamine (indirect agonist)
● 2 inside cell● Magnesium (inverse agonist)● PCP (inverse agonist)
NMDA 'AND' Gate● Detects correlation
between inputs from different cells
● Mediates long term potentiation (LTP)
depolarization Glu Glycine
Opens Ca++ channel
Open channel pore
Removes Mg++
GABA (Gamma Aminobutyric Acid)
• Principal Inhibitory NT• Biosynthesis:
• Removed by reuptake• 2 receptor types
• GABAA (ionotropic)
• GABAB (metabotropic)
Glu GABAGlutamic Acid
Decarboxylase (GAD) and B6
GABAa Binding Sites
● GABA● Muscimol (direct agonist); bicuculine (direct antagonist)
● Benzodiazepine (indirect agonist)● Natural inverse agonist binds
here (fear, tension, anxiety)● Tranquilizing drugs
(anxiolytics): valium, librium● Likely site for alcohol
● Barbiturate (indirect agonist)● Phenobarbital; pentobarbital
● Steroid (indirect agonist)● Picrotoxin (inverse agonist): causes convulsions
Acetylcholine● First NT discovered● Mostly excitatory effects● Neuromuscular Junction
Removal:
Acetyl CoA+
Choline
CoA+
AChCholine Acetyltransferase (ChAT)
AchAcetate
+CholineAcetylcholine
Esterase (AChE)
• 2 receptor types• Nicotinic (ionotropic)• Muscarinic (metabotropic)
Synthesis:
ACh Receptors● Muscarinic
– Smooth Muscles (heart & eye)
● Agonized by muscarine– Amanita muscaria
● Antagonized by atropine– Alkaloid from Atropa
belladona
ACh Receptors● Nicotinic
● Skeletal muscles (neuro-muscular junction)
● Agnoized by nicotine● Antagonized by curare
Ayahuasca● Psychedelic brew
used by Shamans in Amazon Basin
● DMT (indolamine)+ MAOI
● Extremely potent 5HT2a agonist
Painting by Pablo Amaringo, Peruvian shaman w/ photographic memory
Serotonin
● Mood, social cognition● Biosynthesis:
Tryptophan 5-HTP 5-HTTryptophanHydroxylase
5-HTDecarboxylase
• At least 9 receptor types, all metabotropic and postsynaptic except:• 5-HT1A,B,D (autoreceptors)
• 5-HT3 (inhibitory, ionotropic)
Major 5-HT Pathways
● Dorsal Raphe Nuclei cortex, striatum● Medial Raphe Nuclei cortex, hippocampus
Roles in:MoodEatingSleep and dreamingArousalPainAggression
Dopamine
● Rewarding effects● Biosynthesis:
Tyrosine L-DOPA DATyrosine
HydroxylaseDOPA
Decarboxylase
• 5 receptor types (D1–D5, all metabotropic)• D1 (postsynaptic)• D2 (pre and postsynaptic)
Major DA Pathways
● Nigrostriatral (Substantia Nigra Striatum) [Motor movement]● Mesolimbic (VTA limbic system) [Reinforcement and Addiction]● Mesocortical (VTA prefrontal cortex) [Working memory and planning]
Norepinephrine
● Arousal, attention● Biosynthesis:
DA NEDopamine
Beta-hydroxylase
• Many receptor types (metabotropic)∀ α1, β1-2 (postsynaptic, excitatory)
∀ α2 (autoreceptor, inhibitory)
Major NE Pathway
● Locus Coeruleus throughout brain [vigilance and attentiveness]
Opioids: General
● Genetically coded, synthesized from mRNA● Colocalized with and modulate effects of other neurotransmitters● Act as neurotransmitters and neuromodulators● Broken down by enzymes (no reuptake)● Usually modulatory/inhibitory
Opioids: Specific
∀ β-endorphin● made from proopiomelanocortin (POMC) ● produced in pituitary gland, hypothalamus, brain stem
● Enkephalin● made from proenkephalin (PENK)● produced throughout brain and spinal cord
● Dynorphin● made from prodynorphin (PDYN)● produced throughout brain and spinal cord
Opioids Receptors
Receptor High affinity ligandsmu β-endorphin, enkephalinsdelta enkephalinskappa dynorphins
• Opioids act at all opioid receptors, but with different affinities
• Distributed throughout brain and spinal cord, especially in limbic areas
• Some overlap but quite distinct localizations
Opioid Receptors continued
● Metabotropic, with either● moderately fast indirect action on ion channels● long-term action via changes in gene
expression
● Most analgesic effects from mu receptor action● Some analgesic effects from delta● Many negative side effects from kappa