Exam 3: Patho of CNS disorders Flashcards
Overall structure of brain
-Forebrain (cerebral cortex, basal ganglia, limbic, diencephalon)
-Midbrain (SN)
-Hindbrain (medulla, pons, cerebellum)
Hindbrain
-medulla
-pons
-cerebellum
Medulla
-hindbrain
-autonomic functions
-respiration, cardiac, vasomotor responses, reflexes
Pons
-hindbrain
-bridge from forebrain to cerebellum
Cerebellum
-hindbrain
-little brain
-motor coordination for smooth movements
-undergoes neurodegeneration in spinocerebellar ataxias (jerky movements)
Midbrain
-substantia nigra (SN)
-SN compacta and reticulata
SN pars compacta
-input to basal ganglia
-supplies dopamine to striatum
-voluntary movement and some cognitive functions (spatial learning)
-undergoes neurodegeneration in PD
SN pars reticulata
-output function
-relays signal from basal ganglia to thalmus
Forebrain
-cortex
-basal ganglia
-limbic system (amygdala, hippocampus)
-diencephalon (hypo/thalmus)
Cortex
-forebrain
-cerebrum
-processing and interpreting info
-executive function
basal ganglia
-forebrain
-striatum (caudate and putamen), globus pallidus, subthalmic nucleus
-voluntary motor control and some cognitive function
limbic system
-forebrain
-amygdala: emotions
-hippocampus: memory
Diencephalon
-forebrain
-thalamus: relay to and from cortex
-hypothalamus: homeostasis, emotions, hormones (pituitary) and direct neural regulation
Cortex and decision making
-info from environment passed through thalamus to cortex and back
-decisions made in CORTICO-THALAMIC loops abt how to interpret and act on incoming sensory info
-damage can affect movement, speech, personality
-schizophrenia is considered disease of frontal cortex
Which of the following structures is directly involved in controlling involuntary functions?
A. Hypothalamus
B. Thalamus
C. Medulla Oblongata
A. Hypothalamus
C. Medulla
KNow diagram structure of brain
Glial cells
-astrocytes
-oligodendrocytes
-microglia
astrocytes
-glial cells
-provide neurons w growth factors and antioxidants
-remove extra glutamate (excitotoxic NT)
-blood-brain barrier
-have extensions and feet wrap around blood vessels
Oligodendrocytes
-glial cells
-produce myelin sheath
=insulate axons
Microglia cells
-glial cells
-provide growth factors
-clear debris (myelin debris) by phagocytosis
-role in NEUROINFLAMMATION
Blood-brain barrier
-stabilized by tight junctions in endothelial layer of blood vessels in brain
-drugs must be SMALL and HYDROPHOBIC (UNCHARGED)
Neurotransmission
-release of synaptic vesicles from boutons into synaptic gap
-triggered by depolarization by influx of Na+ ions
Polarized state of neuron
-negative on inside
-positive on outside
Normal action potential
-resting potential
-influx of Na = upstroke to overshoot
-repolarization dec back to rest
-hyperpolarization: dips below resting potential during repolarization
-depolarization: brings potential back to resting state
-lasts 0.2-0.5 ms
Refractory period
-hyperpolarized phase after repolarization where neuron won’t fire again
Neuron Firing
-action potentials are all same magnitude
-degree of activity determined by frequency of action potential
-excitatory, depolarizing = inc freq
-inhibitory, polarizing = dec freq
excitatory postsynaptic potential (ESP)
-induced by excitatory NTs
-subthreshold depolarization peak
-cant get above threshold to signal so it just dies out
-excitatoty NTs let Na cross membrane
-inc in strength of timulus will inc magnitiude of depolarization so that threshold can be achoeved?
inhibitory postsynaptic potential (IPSPs)
-induced by inhibitory NTs
-inhibitory NTs allow Cl ions across membrane
=HYPERpolarization
-IPSP can dec magnitude of subsequent EPSP
GRaphs
-slide 16-19
Slide 21 figure
NEED to know
By what mechanisms do drugs act on CNS
-(anta)gonists at synaptic receptors
-target metabolism, reuptake, transport to glial cells
Common amino acid neurotransmittors
-GABA (inhibitory)
-glycine (inhibitory)
-glutamate (excitatory)
Gamma aminobutyric acid (GABA)
-inhibitory
-amino acid NT
-throughout brain
-role in epilepsy, spasticity, addiction
GABA mech
-GABA(A) ion channel
-GABA(B,C) GPCR
-dec excitability by inc Cl influx into neuron
GABA plays a role in
-epilepsy
-spasticity
-addiction
drugs that interact w GABA pathways are usually:
-CNS depressants
-sedative hypnotics (benzos, barbituates)
-anticonvulsants
-anxiolytics
Glycine
-inhibitory
-amino acid NT
-similar to GABA but in spinal cord
Glutamate
-excitatory
-amino acid NT
-throughout brain
-role in epilepsy and schizophrenia
-xs = neural damage
Glutamate receptors
-mGluR metabotropic GPCR
-NMDA and AMPA ion channels
excess glutamate
-can cause neuronal damage by allowing xs Ca influx
Glutamate plays a role in
-epilepsy
-schizophrenia
Non-amino acid NTs
-acetylcholine
-dopamine
-norepinephrine
-serotonin
Acetylcholine
-basal forebrain, pons, cortex, basal ganglia
-nicotinic (nAChR) and muscarinic M1-M5 (mAChR) receptors
-cognitive function, nicotine dependence, movement disorders
Acetylcholine location
-basal forebrain
-pons
-cortex
-basal ganglia
Acetylcholine plays a role in
-cognitive function/decline
-nicotine dependence
-movement disorders
ex of drug targetting acetylcholine
-cholinesterase inhibitors
-Aricept for Alzheimer’s
Dopamine
-midbrain (arise from SN, VTA)
-D1-D5 and DAT (transporter)
-schizophrenia, PD, addiction, depression, ADHD
Dopamine location
-midbrain
-arise from ventral tegmental area (VTA) and SN)
Dopamine receptors
-D1-D5 GPCRs (1: Gs, 2: Gi)
-dopamine transporter (DAT)
Dopamine plays role in
-schizophrenia (xs signaling)
-parkinson’s (loss of dopamine)
-addiction (xs)
-depression, ADHD
Drugs and dopamine
-block DAT = euphoria/addiction (cocaine, amphetamine)
-antipsychotics are D2 ANTAgonists
-use D1 and D2/D3 agonists to tx parkinsons
Norepinephrine
-pons (locus coeruleus)
-a and B adrenergic receptors (GPCR)
-NE transporter (NET)
-memory, depression, addiction, pain
norepinephrine location
-arise from locus coeruleus in pons
NET inhibitors
-treat depression
Serotonin, 5-hydroxytryptamine (5-HT)
-midbrain/pons (raphe nuclei)
-14 GPCRs, 1 ion channel, 1 transporter (SERT)
-depression, mood, schizophrenia
-sleep, vigilance, mood, sexual function
Drugs that interact with 5-HT receptors
-5-HT2a ANTAgonists = atypical antipsychotics
-SERT inhibitors for depression
-5-HT2A AGONists are hallucinogens (LSD)
serotonin (5HT) location
-midbrain/pons
-arise from raphe nuclei (group of cell bodies)
