MODULE 2 | CNS Flashcards
controls voluntary muscles
SOMATIC NS
controls involuntary muscle
AUTONOMIC NS
AUTONOMIC NS
arouses body to expend energy
SYMPATHETIC NS
AUTONOMIC NS
calms body to conserve & maintain energy
PARASYMPATHETIC NS
electrically excitable cells that process and transmit information via an electrochemical process
NEURONS
- highly branched complex “trees”
- receive & integrate the input from other neurons & conduct this information to the cell body
DENDRITES
- carries the output signal of a neueron from the cell body, sometimes over long distances
- only one in every neuron, but may branch distally to contact multilpe targets
AXONS
- makes contact with other neurons at specialized junctions called synapse
AXON TERMINAL
- specialized junctions/spaces
- where neurotransmitter chemicals are released that interact with receptors on other neurons
SYNAPSES
2 BROAD CATEGORIES OF NEURONAL SYSTEM IN CNS
- Heirarchial system
- Nonspecific / Diffuse Neuronal system
NEURONAL SYSTEM
- include all pathways directly involved in sensory perception and motor control
HIERARCHICAL SYSTEM
NEURONAL SYSTEM | HIERARCHICAL
____ at any link incapacitates the system
lesion
NEURONAL SYSTEM | HIERARCHICAL
in ____ system, information is processed sequentially by successive integrations at each relay nucleus on its way to the cortex
sensory system
2 types of Hierarchical system
- Relay / Projection
- Local circuit
HIERARCHICAL CELLS
- relatively large axons
- emit collaterals that arborize extensively in the vicinity of the neurons
- excitatory
- glutamate
- interconnecting pathways transmit signals over long distances
RELAY / PROJECTION
HIERARCHICAL CELLS
- small axons
- arborize in the immediate vicinity of the cell body
- inhibitory
- GABA / Glycine
- recurrent feedback pathways and feed-forward pahtways
LOCAL CURCUIT
primary inhibitory nuerotransmitter in the brain
GABA
major excitatory transmitter
GLUTAMATE
primary inhibitory nuerotransmitter in the spinal cord
GLYCINE
NEURONAL SYSTEM
- include the Dopamine, Serotonin, Norepenephrine, Acetylcholine
- some peptide-containing pathways
- small, approx 1500 on each side of the brain (rat)
- axons are very fine and unmyelinated
- NT: monoamines
- RECEPTORS: adrenergic receptros (metabotropic, type 2)
- implicated in functions such as sleeping, waking, attention, appetite, and emotional states
NONSPECIFIC / DIFFUE NERUONAL SYSTEM
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
include ____, ____, ____, ____
dopamine
serotonin
norepenephrine
acetylcholine
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
found in compact cell group called locus coeruleus located in the caudal pontine central gray matter
NE cell bodies
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
axons are ____ & ____
very fine & unmyelinated
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
neurotransmitters
monoamines
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
receptors
adrenergic receptors
metabotropic, type 2
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
pathways emanating from ____
reticular formation
NEURONAL SYSTEM | NONSPECIFIC / DIFFUSE
reticular formation is often found in the
brain stem
CNS always act on what channel
ion-channel
explains the mehcanism of impulse transport across the synapse
SYNAPTIC NEUROTRANSMISSION
presence of gaps or spaces
synapse
nervous system is ____
discontinuous
PARTS OF SYNAPSE
- synthesis, storage (vesicles), release or exocytosis of neurotransmitter
- has enzymes: metabolism of NT
- has autoreceptors: inhibitory effect
PRESYNAPSE
PARTS OF SYNAPSE
- has enzymes: metabolism
CLEFT
PARTS OF SYNAPSE
- has the majority of receptors: excitatory effect
- enzymes: metabolism
POST SYNAPSE
INHIBITORY neurotransmitter
DOPAMINE
GABA
GLYCINE
SEROTONIN
EXCITATORY neurotransmitter
ACETYLCHOLINE
NOREPENEPHRINE
GLUTAMATE
SYNTHESIS OF ACETYLCHOLINE
precursor that must be actively transported into neurons for acetylcholine synthesis
CHOLINE
SYNTHESIS OF ACETYLCHOLINE
transport of choline is inhibited by ____
hemicholinium
SYNTHESIS OF ACETYLCHOLINE
Ach binds to what receptor
muscharinic
SYNTHESIS OF ACETYLCHOLINE
protects the Ach from the metabolism/degradation
uptake into storage vesicles
SYNTHESIS OF ACETYLCHOLINE
the release of neurotrnasmitter is blocked by ____
botulinum toxin
SYNTHESIS OF ACETYLCHOLINE
causes the release of Ach
sppider venom
a-latrotoxin
SYNTHESIS OF ACETYLCHOLINE
spider venom is also known as
a-latrotoxin
SYNTHESIS OF ACETYLCHOLINE
postsynaptic receptor is activated by ____
binding of the NT
has no direct reuptake to presynapse
acetylcholine
SYNTHESIS OF ACETYLCHOLINE
Ach needed to be ____ to be uptaken to presynapse
choline
SYNTHESIS OF ACETYLCHOLINE
Ach is rapidly hydrolyzed by ____ in the synaptic cleft
acetylcholinesterase
SYNTHESIS OF ACETYLCHOLINE
which can enhance Ach levels
anticholinesterases
SYNTHESIS OF ACETYLCHOLINE
ion needed for the release of Ach to the cleft
Calcium ion
SYNTHESIS OF ACETYLCHOLINE
converts acetylcholinesterase into choline & acetate
acetylcholinesterase
SYNTHESIS OF NOREPENEPHRINE
NE binds to what receptors
adrenergic
SYNTHESIS OF NOREPENEPHRINE
rate limiting step
hydroxylation of tyrosine
ENDogenous cathecolamines
Epinephrine
Norepenephrine
Dopamine
SYNTHESIS OF NOREPENEPHRINE
product of hydroxylation of tyrosine
rate-limiting step
L-DOPA
SYNTHESIS OF NOREPENEPHRINE
enzyme in hydroxylation of tyrosine
conversion of tyrosine → L-DOPA
tyrosine hydroxylase
SYNTHESIS OF NOREPENEPHRINE
inhibits the enzyme tyrosine hydroxylase
metyrosine
SYNTHESIS OF NOREPENEPHRINE
sequence of kineme
tyrosine
↓
L-DOPA
↓
dopamine
↓
norepenephrine
SYNTHESIS OF NOREPENEPHRINE
responsible for the transport of the monoamine NT (DE) to the vesicle
VMAT - vesicular monoamine transporter
SYNTHESIS OF NOREPENEPHRINE
the transport of dopamine to the vesilce is inhibited by
reserpine
SYNTHESIS OF NOREPENEPHRINE
dopamine enters the vesicle and is converted to ____
norepenephrine
SYNTHESIS OF NOREPENEPHRINE
causes fusion of the vesicles with the cell membrane in a process known as exocytosis
influx of calcium
SYNTHESIS OF NOREPENEPHRINE
release ENHANCERS
Thyramine
Ephedrine
Amphetamine, Angiotensin II
Methampethamine
Tatay (THY) Efren (EPH) AMP si ANGel may METH
SYNTHESIS OF NOREPENEPHRINE
release INHIBITORS
Guanadrel
Guanethedine
Bretylium
SYNTHESIS OF NOREPENEPHRINE
the release of the NE from the vesicle is a process called
exocytosis
SYNTHESIS OF NOREPENEPHRINE
NE is synthesized in the
vesicle
SYNTHESIS OF NOREPENEPHRINE
NE is diffused into ____ where epinephrine is synthesized
adrenal medula
SYNTHESIS OF NOREPENEPHRINE
what does MAO inhibitor do
enhances the NE levels
SYNTHESIS OF NOREPENEPHRINE
reuptake INHIBITORS
Cocaine
Atomoxetine
Sibrutamine
Imipramine
COl mo na si ATO SIBihin mo IMIP na ako
SYNTHESIS OF NOREPENEPHRINE
reuptake inhibitors ____ the effect of NE
increases/enhances
SYNTHESIS OF NOREPENEPHRINE
breaks down NE, SE, EPI
MAO A
SYNTHESIS OF NOREPENEPHRINE
breaks down DA
MAO B
neurotransmitter that is associated with Parkinson’s disease and increased prolactin hormone
DOPAMINE
chemicals that take a nerve signal across the synaptic gap beetween a sending neuron and a recieveing one
neurotransmitters
2 GROUPS OF NEUROTRANSMITTERS
- classical
- neuropeptide NTs
2 GROUPS OF NEUROTRANSMITTERS
- small molecule NTs
- mainly amino acids and amines
CLASSICAL
2 GROUPS OF NEUROTRANSMITTERS
- relatively larger
- combination of two or more amino acids joined by peptide bonds
NEUROPEPTIDE NTs
AMINO ACID NTs
- acidic amino acid
- excitatory
GLUTAMATE
AMINO ACID NTs
- neutral amino acid
- inhibitory
GLYCINE
GABA
does GLUTAMINE have direct reuptake or no
no
GLUTAMATE → GLUTAMINE → GLUTAMATE
enzymes: glutamine synthetase, glutaminase
AMINO ACID NTs
- released into the synaptic cleft by Ca-dependent exocytosis
- meediates excitatory post synaptic transmission
- vesicular glutamate transporter (VGLUT)
- activates both ionotropic and metabotropic receptors
- all are composed of four subunits
GLUTAMATE
AMINO ACID NTs | GLUTAMATE
released into the synaptic cleft by
Ca-dependent exocytsosis
AMINO ACID NTs | GLUTAMATE
mediates ____ post synaptic transmission
excitatory
AMINO ACID NTs | GLUTAMATE
activates what kind of receptors
both ionotropic & metabotropic
AMINO ACID NTs | GLUTAMATE
how many subunits
4
GLUTAMATE IONOTROPIC RECEPTORS
- GluA1 - GluA4 subunits
- majority contain GluA2 subunit and permeable to Na and K but not to Ca
- some are present on inhibitory interneurons, lack the GluA2 subunit and are also permeable to Ca
AMPA
GLUTAMATE IONOTROPIC RECEPTORS
AMPA subunits
GluA1 - A4
GLUTAMATE IONOTROPIC RECEPTORS
AMP are permeable to
Na & K
GLUTAMATE IONOTROPIC RECEPTORS
AMP are not permeable to
Ca
GLUTAMATE IONOTROPIC RECEPTORS
- high levels in the hippocampus, cerebellum, and spinal cord
- formed from a number of subunit combinations (GluK1-K5)
- permeable to Na and K and in some subunit combinations can also be permeable to Ca
KA (Kainate) Receptor
GLUTAMATE IONOTROPIC RECEPTORS
- present on essentially all neurons in the CNS
- highly permeable to Ca as well as to Na and K
NMDA
GLUTAMATE IONOTROPIC RECEPTORS
NMDA receptor channel opening:
____ must bind the receptor
GLUTAMATE
GLUTAMATE IONOTROPIC RECEPTORS
NMDA receptor channel opening:
membrane must be ____
depolarized
act indirectly on ion channels via G protein
G protein-coupled receptors
GLUTAMATE METABOTROPIC RECEPTORS
- typically located postsynaptically (excitatory)
- activate phospholipase C, leading to inositol triposphate mediated intracellular Ca release
GROUP I
GLUTAMATE METABOTROPIC RECEPTORS
what does Group 1 receptors activate
phospholipase C
GLUTAMATE METABOTROPIC RECEPTORS
- typically located on presynaptic nerve terminals and act as inhibitory autoreceptors
- activation causes the inhibition of Ca channels, resluting in inhibition of transmitter release
- are activated only when the concentration of glutamte rises to high levels during repetitive stimulation of the synapse
- activation also causes the inhibition of adenylyl cyclase and decreases cAMP generation
GROUP II & III receptors
AMINO ACID NTs
inhibitory NTs typically released from local interneurons
GABA
GLYCINE
AMINO ACID NTs
- selectively permeable to Cl
GLYCINE
AMINO ACID NTs | GLYCINE
____ selectively blocks glycine repectors
STRYCHNINE
AMINO ACID NTs
- ionotropic receptor that are selectively permeable to Cl
- mediate fast component of IPSP
GABA A
AMINO ACID NTs
ion channels associated with GABA A
chloride channels
AMINO ACID NTs
- metabotropic receptors, selectively activated by Baclofen (GABA B agonist)
- inhibit Ca channel or activate K channel
- also inhibit adenylyl cyclase and decrease cAMP generation
GABA B
AMINO ACID NTs
GABA B agonist
Baclofen
- first compound to be identified pharmacologically as a transmitter in the CNS
- responses are mediated by both muscarinic and nicotinic receptors
- degraded by cholinesterases
- presenile dementia of the Alzheimer type is reportedly associated with a profound loss of cholinergic neurons
ACETYLCHOLINE
ACETYLCHOLINE
responses are mediated by what receptors
muscarinic & nicotinic
ACETYLCHOLINE
which has slower effects?
NICOTNIC or MUSCARINIC
muscarinic
ACETYLCHOLINE
CNS responses are mostly mediated by ____
GPC muscarinic receptors
ACETYLCHOLINE
degraded by
cholinesterases
ACETYLCHOLINE
8 major CNS nuclei of Ach neurons have been characterizedd with ____
diffuse projections
a target for management of Alzheimer’s disease
anticholinesterase
low acetylcholine levels
Alzheimer
what to do to increase the levels of Ach
inhibit cholinesterases
MONOAMINES
Catecholamines: DA, NE
Serotonin
Histamine
MONOAMINES
serotonin is also known as
5-hydroxytryptamine
5-HT
MONOAMINES
Norepenephrine is also known as
noradrenaline
MONOAMINES
energy expanding
Ergotrophic vigilance
NE
MONOAMINES
energy conserving
Trophatrophic
SE
MONOAMINES
pleasure drive
DA
MONOAMINES
- most noradrenergic neurons are located in the locus coeruleus or the lateral tegmental area of the reticular formation
- an amine, excitatory transmitter of the brain and smooth muscle
- metabotropic
- hyperpolarizes the neuron by increasing potassium conductance via the Alpha-2 receptor (GI - inhibitory)
- enhances excitatory inputs in most areas of the CNS by both indirect and direct mechanisms
- induce arousal, heighten mood
- impaired monoamine has been associated with depression
NOREPENEPHRINE
MONOAMINES | NOREPENEPHRINE
most noradrenergic neurons are located in the
locus coeruleus
MONOAMINES | NOREPENEPHRINE
excitatory transmitter of the ____ and _____
brain & smooth muslce
MONOAMINES | NOREPENEPHRINE
all receptors are ____
metabotropic
MONOAMINES | NOREPENEPHRINE
mechanism involves disinhibition
indirect mechanism
MONOAMINES | NOREPENEPHRINE
mechanism involves blockade of potassium conductance
direct mechanism
MONOAMINES | NOREPENEPHRINE
impaired monoamine neurotransmission has been associated with ____
depression
MONOAMINES | NOREPENEPHRINE
drugs that induce monoamine release are indicated for ____ and ____
attention deficit disorder (ADHD) and narcolepsy
MONOAMINES
- synthesized from L-dopa
- degraded by monoamine oxidase A in the brain and MAO B outside the CNS by catechol-O-methyl transferase (COMT)
- receptors are all metabotropic
- major pathways are the projection linking the substantia nigra to the neostriatum and the projection linking the ventral tegmental region to limbic structures, particularly the limbic cortex
- generally exerts a slow inhibitory action on CNS neurons
- best characterized on dopamine-containing substantia nigra neurons, where D2 receptor activation opens potassium channels via the GCP
DOPAMINE
MONOAMINES | DOPAMINE
synthesized from ____
Ldopa
MONOAMINES | DOPAMINE
degraded by
major degradator
MAO B
MONOAMINES | DOPAMINE
all receptors are ____
metabotropic
MONOAMINES | DOPAMINE PATHWAYS
substantia nigra to striatum
NIGROSTRIATAL PATHWAY
MONOAMINES | DOPAMINE PATHWAYS
controls vomiting
chemoreceptor trigger zone (CTZ) of the medulla
MONOAMINES | DOPAMINE PATHWAYS
regulate prolactin release
hypothalamus to intermediate lobe ofpituitary
a monoamine that can induce vomiting and can inhibit prolactin release
DOPAMINE
DOPAMINE DISORDERS
result from overstimulation of dopamine receptors
too much dopamine in cytosis
PSYCHOSES
DOPAMINE DISORDERS
caused by too little dopaminergic input from the substantia nigra into the striatum
low dopamine levels
PARKINSON’S DISEASE
MONOAMINE
- formed from tryptophan (hydroxylated then carboxylated)
- released from inhibitory neurons
- stimulates 5HT receptors
- all receptors are metabotropic, except 5HT3 (ionotropic)
- has inhibitory actions in most areas of the CNS
- has been implicated with the regulation of virtually all brain functions
- depression, attention deficit disorder, and headaches have been attributed to its imbalance
SEROTONIN, 5HT
MONOAMINE | SEROTONIN
formed from ____
tryptophan
MONOAMINE | SEROTONIN
released from ____
inhibitory neurons
MONOAMINE | SEROTONIN
ionic receptor
5HT3
MONOAMINE | SEROTONIN
disorders that have been attributed to serotonergic imbalance
depression
ADHD
headahce
MONOAMINE
- exclusively made by neurons in the tuberomammillary nucleus (TMN) in the posterior hypothalamus
- modulate arousal, attention, feeding behavior, and memory
- H1 - H4
- metabotropic
- centrally acting are generally used for their sedative properties
- antagonism of H1 receptors is a common side effect of many drugs including some tricyclic antidepressants and antipsychotics
HISTAMINE
MONOAMINE | HISTAMINE
exclusively made by neurons in the ____
tuberomammillary nucleus (TMN)
MONOAMINE | HISTAMINE
antacid receptor
H2
MONOAMINE | HISTAMINE
antihistamine receptor
H1
MONOAMINE | HISTAMINE
centrally acting antihistamines are generally used for their ____ properties
sedative
MONOAMINE | HISTAMINE
antagonism of ____ receptor is a common side effect of many drugs
H1
- generally packaged in large, dense core vesicles
- released neuropeptides may act locally or may diffuse long distances and bind to distant receptors
- metabotropic and primarily serve modulatory roles in the NS
- implicated a wide range of CNS functions: reproduction, social behaviors, appetite, arousal, pain, reward, learning, & memory
NEUROPEPTIDES
NEUROPEPTIDES
- endorphines, enkephalins, & dynorphins
- metabotropic - mu, kappa, delta
- in times of stress and pain, endogenous peptides act to relieve pain
OPIOIDS
opioid analgesic
morphine
NEUROPEPTIDES
- released from primary sensory neurons in the spinal cord and brainstem and causes a slow excitatory postsynaptic potential
- plays an important role in transmitting pain stimuli
SUBSTANCE P
P - pain
- peptide NTs produced in the lateral and posterior hypothalamus
- also called hypocretins
- bind to two GPCR, OX1 & OX2
- excitatory
- associated with wakefulness
- project to and activate monoamine and acetylcholine neurons involved in sleep-wake cycles
- also involved in energy homeostasis, feeding behaviors, autonomic function, and reward
OREXIN
OREXIN
are also called as
hypocretins
OREXIN
two GPCR that it binds to
OX1 & OX2`
OREXIN
associated with
wakefulness
OREXIN
involved in
sleep-wake cycles
OREXIN
animals lacking orexin or its receptor have ____ and ____
narcolepsy
disrupted sleep-wake patterns
OTHER SIGNALLING SUBSTANCES
- endogenous cannabinoids can function as retrograde synaptic messengers
- released from postsynaptic neurons and travel backward across synapses, activating CB1 receptors on presynaptic neurons and suppressing transmitter release
- cannabinoids may affect memory, cognition, and pain perception
ENDOCANNABINOIDS
OTHER SIGNALLING SUBSTANCES
- generated when neuronal nitric oxide synthase (NOS) is activated by calcium-calmodulin and activation of NMDA receptors - increases intracellular calcium
- longterm depression of synaptic transmission in the cerebellum
NITRIC OXIDE
OTHER SIGNALLING SUBSTANCES
- ATP found in and released from catecholinergic synaptic vesicles, and may be converted to adenosine extracellulary by nucleotidases
- adenosine in the CNS acts on metabotropic A1 receptors
- Presynpatic A1 receptors inhibit calcium channels and inhibit release of both amino acid and monoamine transmitters
- involved in memory, wakefulness, and appetite, and may play roles in multiple neuropsychiatric disorders
PURINES
OTHER SIGNALLING SUBSTANCES | PURINES
nonselective ligand-gated cation channels
P2X
OTHER SIGNALLING SUBSTANCES | PURINES
metabotropic
P2Y
