Introduction to CNS - Kelly 2 Flashcards
Blood brain barrier
Isolates CNS
Modified endothelial cells with light junctions: lipophilic things can pass, but ionic charged substances can’t
Lack of leakage
Astroglial process and pericytes
Highly lipophilic
BBB can be affected during injury or infection
Neuronal systems involved in
Cognitive processing Memory Emotional processing Sensory processing Motor processing Autonomic Processing
CNS neurotransmission
Depolarization at nerve terminal
Ca enters through channels
Promotes fusion of vesicles with nerve terminal to allow release
NT can be taken back or degraded
Sensitization of receptors
Sustained reduction in NT release or long term use of antagonist
Sensitized response when antagonist is taken away
Up regulation
Desensitization
Sustained blockade of NT reuptake or long term use of agonist
Receptor down-regulation: internalized
Important CNS receptors
Voltage gates
Ligand-gated ion channels
Membrane delimited metabotropic ion channel
Diffusible second messager metabotropic ion channel
Voltage gages ion channel
Ions moved based on what is favourable for voltage of cell
Pore is lined with charged amino acids
Voltage affects aa and they move to expose different areas
Facilitate opening that certain ions can move through
Ligand-gated ion channel
Inotropic channel
Channel is gated by binding of one, two or more ligands
Diffuse second messager metabotropic ion channel
Diffusible messenger activated ion channel
Excitatory membrane potential
Reaching AP
Conducted along axons and evoke NT release from nerve terminal
If enough EPSPs, AP will happen
Inhibitory membrane potential
Usually hyper polarizes the cell membrane and inhibits AP formation and can decrease NT release
Long tract cellular organization
Messages over long distances
Motor control
Relay, projection neurons
Local circuit cellular organization
Short, modulation
Shape recognition in the optic tract
Interneurons
Divergent
Widely projecting neurons
Global functioning
Sleep-wake cycles
Diffuse system
CNS neurotransmitters
Amino acids Acetylcholine Monoamines Peptides Endocannabinoids
Criteria for a NT
Must be present in a higher concentration in the synapse than in other areas (localized)
Released by electrical or chemical stimulation via Ca-dependent mechanism
Produce a post-synaptic response similar to nerve stimulation (synaptic mimicry)
Mechanism for termination of transmitter action
Amino acids
High concentration in the CNS
Potent
Excitatory: glutamate
Inhibitory: GABA, glycine
Glutaminase
Converts glutamine to glutamate
Glutamate decarboxylase
Converts glutamate to GABA
Glutamate
Major excitatory NT in CNS
Inotropic and metabotropic receptors
Termination by glia uptake, where it is converted to glutamine
Inotropic glutamate receptors
NMDAR, AMPAR, KAR
Metabotropic glutamate receptors
mGLUR1
Postsynaptic (Gq) and presynaptic (Gi)
NMDAR
Very calcium permeable when open
Reenforcement of Ca circuit
Do not like to be opened, at rest blocked by Mg
Need huge depolarization to be activated (summation)
Glu opens AMPAR non-selective ion channels which allows for further depolarization and dissociation of Mg
GABA
Inhibitory
Inotropic (GABAA, Cl) and metabotropic (GABAB, Gq)
Widely expressed
GABAB can be presynaptic
Ligand gated ion channel, binds between 2 subunits of pentameric structure
Allosteric modulators need orthosteric activity
Direct activation of K channel
Glycine
Inhibitory
Inotropic (Cl)
Limited expression: interneurons in SC and brainstem
Acetylcholine
Ionotopic (nicotinic) Metabotropic (muscarinic) Excitatory, inhibitory Widely expressed Cognitive functions Target in treatment of Alzheimers disease
Aceyltransferase
Convers AcCoA to acetyl choline
Muscarinic receptors
M1, M3, M5: Gq, increase IP3, DAG, decrease cAMP, gK
M2, M4: ion channel, increase gCa, gK, GNa
Monoamines
Dopamine, norepinephrine, serotonin (5-HT)
Derived form aa
Synthesis enzyme/neuron dependent
Small amounts
Complex functions: alertness, consciousness
Dopamine
5 known receptors D1 or D2 Metabotropic Inhibitory Diffuse Target in Parkinson's disease L-Tyrosine to DOPA to dopamine Behaviour, drug reenforcement, emesis, hormone release, mood, motor coordination, olfaction
Tyrosine hydroxylase
Converts L-tyrosine to DOPA
L-amino acid decarboxylase
Converts DOPA to dopamine
D1, D5
Excitatory
Gs, Gq
Increase cAMP, IP3, DAG, Ca
D2, D3, D4
Inhibitory
Gi/o
Decrease cAMP, K, VDCC
Norepinephrine
Adrenergic receptors alpha and beta: metabotropic
Excitatory
Diffuse
Attention, arousal
Dopamine converted into norepinephrine by dopamine P hydroxyase
Anxiety, learning, memory, mood, sensory, processing, sleep
Dopamine P hydroxylase
Converts dopamine to norepinephrine
A1 receptor (NE)
Gq
Increase IP3, DAG, Ca
A2 R (NE)
Gi
Decrease cAMP
B1, B2 (NE)
Gs
Increase cAMP
Serotonin
15 5-HT receptors (metabotropic) except 5-HT3 which is inotropic
Tend to be inhibitory
Diffuse
Sleep, temperature, appetite, neuroendocrine control
Target in treatment of affective disorders
Tryptophan hydroxylase
Converts tryptophan to 5-hyroxytryptophan, which is converted to 5-hydroxytryptoamine by LAAD
Neuropeptides
Many Opioids (endorphins, enkephalins) Pain sensation Target of analgesics, drugs of abuse Metabotropic Can be released in conjunction with other NTs Differ from non-peptide transmitters: 1. Synthesized in cell body and transported to nerve ending 2. No reuptake or enzyme degradation
Endocannabinoids
Rapidly synthesized and not stored Act on presynaptic receptors Cannabinoid receptor 1 Suppress NT release Memory, cognition, pain perception
Endocannabinoid signalling
Retrograde messaging
Synthesized by Ca depended enzymes and released from postsynaptic neurons
Signal travels retrogradely across synapse acting CB1R on presynaptic nerve terminal, inhibiting Ca channels
Results in suppression of NT release
NO
Gas formed from arginine by NO synthase in CNS neurons
May participate in retrograde NT and LTP
Leptin/Orexin
Hormone modulators formed in hypothalamus
Important in regulation of appetite
Purines
Adenosine and ATP
activate specific purinergic receptors: evidence that ATP is a cotransmitter
