neurotransmitters Flashcards
overview of direct synaptic transmission
neurotransmitter release -> receptor binding -> ion channels open or close -> conductance change causes current flow -> postsynaptic potential changes (EPSP or IPSP) -> summation and threshold -> action potential or no action potential
3 features of transmitters
- presence in presynaptic neuron
- calcium dependent release when presynaptic neuron depolarizes
- specific receptors for the substance must be present on the postsynaptic cell
dale’s principle
thought that one nerve was only responsible for releasing one neurotransmitter
proven wrong
3 basic groups of neurotransmitters
“classic” low-molecular weight
gases
neuropeptides
life cycle of neurotransmitter
- synthesis
- storage
- release
- postsynaptic effects
- inactivation
classic low-molecular weight/small-molecule transmitters
synthesized in axon terminals, packaged in small vesicles, and stored there until release
gases
synthesized in nerve terminals
cannot be stored in cells
highly lipid and water soluble
neuropeptides
synthesized in soma
processed and packaged in large dense-core vesicles in the Golgi
transported to axon terminal
steps of transmitter release
presynaptic depolarization -> Ca2+ entry -> transmitter release
- vesicles fuse with plasma membrane and release contents into synaptic cleft via exocytosis
ionotropic
direct
metabotropic
indirect
3 mechanisms of inactivation of neurotransmission
- diffusion
- degradation
- reuptake (into glia, or nerve terminals), not for neuropeptides
acetylcholine
- most comes from septal nuclei and basal forebrain
- important for learning, memory, and other cognitive processes (attention and decision making)
- evolved defense that targets Ach transmission
ach agonist
nicotine
- highly reinforcing, calming, increases concentration
ach antagonist
scopolamine
- muscarinic antagonist, prevents the ability of medial temporal lobe structures to encode memory
acetylcholinesterase/cholinesterase
enzyme that breaks down ach
alzheimer’s disease
one cause is a reduction of cholinergic neurons in the midbrain, leading to reduced availability of ach in the mediation of memory processes
also characterized by accumulation of neurofibrillary tangles or extracellular plaques that are insoluble and block the projection of cholinergic projections
structure of metabotropic receptors
have similar transmembrane structure as ionotropic receptors but lack pores to conduct ions
instead ligand binding triggers intracellular signaling via g-proteins
areas of the brain more involved with neurotransmission
mostly in striatum and frontal cortex
tracing of neurotransmitters
- neurons using a specific transmitter can be identified by the presence of the transmitter itself, or tagging proteins involved in any step of its life cycle
- mapping by immunohistochemistry and fluorescence probe-tagging, then imaging with electron microscopy
- radio-labeled probes (autoradiography) following in situ hybridization with antisense oligonucleotides for certain receptor subunits
critical excitatory and inhibitory transmitters
- gamma-aminobutyric acid (GABA)
- glycine
- glutamate
glutamate
- primary excitatory transmitter in the brain
- synthesis: mostly derived from glutamine taken into the presynaptic terminal
- storage: vesicular glutamate transporters (VGLUT) load glu into synaptic vesicles
- inactivation: clearance from synaptic cleft by reuptake proteins (GLAST, EAAT, GLT-1, mostly into glial cells)
ionotropic glutamate receptors
NMDA, AMPA, kainate
metabotropic glutamate receptors
8 members in 3 classes
gamma-aminobutyric acid (GABA)
- primary inhibitory transmitter
- synthesis: from glutamate via glutamic acid decarboxylase with pyridoxal phosphates as a co-factor
- storage: transporters bring into synaptic vesicles
- release: at inhibitory synapses, many are interneurons, but the primary projection neurons in the cerebellum and striatum use GABA
- inactivation: high-affinity transporters in presynaptic terminals and glia
biogenic amines (monoamines)
regulate many brain functions and are also active in the pns
involved in mood and affect motivation, attention, and arousal
neurons releasing them are typically localized into small groups in the brainstem
catecholamines
made of a catechol and amine
- epinephrine, norepinephrine, dopamine
- synthesis: in presynaptic terminals (enzymes arrive via axonal transport, precursors are generally taken up directly by presynaptic terminals)
- storage: usually small clear vesicles
- release: calcium dependent vesicle fusion
- receptors: metabotropic
- inactivation: enzymatic degradation and re-uptake transporters
dopamine
dopamine neurons are localized in the brainstem structures substantia nigra and ventral tegmental area
dopamine neurons respond to
- unexpected delivery of reward
- cues that precede rewards
- pause when expected rewards do not occur
- reward prediction error
norepinephrine
involved in wakefulness, attention and feeding behaviors
localized in the midbrain and send widespread and diffuse projections to much of the rest of the brain
respond to alerting stimuli
epinephrine
localized in brainstem/midbrain/thalamus
5-hydoxytryptamine (5-HT)/serotonin
involved in sleep, wakefulness and mood
localized in the pons and upper brainstem, widespread functions to the forebrain
- synthesis: 2 step process starting with tryptophan in the brainstem
- storage: vesicles
- inactivation: uptake by specific serotonin transporter
- receptors: one ionotropic, multiple metabotropic, target of hallucinogens such as LSD
antagonists of ATP
caffeine
theophylline
5 categories of peptide neurotransmitters
- brain-gut peptides (substance P: pain)
- opioid (enkepahlin, endorphins: analgesia, euphoria)
- pituitary (vasopressin, oxytocin: bonding, lactation)
- hypothalamic (LH: sex)
- miscellaneous (Neuropeptide Y: energy balance, eating)
endocannabinoids
heavily expressed in striatum (motivation), substantia nigra (dopamine neurons), hippocampus (memory and spatial location), cerebellum (movement)
- unconventional bc: postsynaptic release, non-vesicular, receptors are pre-synaptic
