Introduction to Central and Peripheral Nervous System Flashcards
How much does the brain weigh?
3 pounds
Roles of CSF
- prevents mechanical damage
- absorbs shock from body movement
- maintains brain ion concentration
What can sampling CSF provide?
Information about drug distribution
AKA does the drug bypass the BBB
- allows us to measure drug conc in brain
CNS
brain and spinal cord
PNS
split into:
Somatic NS and Autonomic NS
Somatic NS
in the PNS
- made up of sensory neurons and motor neurons
- responsible for sending the environment, controlling voluntary movements and reflexes
Autonomic NS
in the PNS
- ‘self-governing’ and controls body’s physiology along with the endocrine system
- split into the parasympathetic and sympathetic NSs (when one is on, the other is off)
Neurotransmitters of the sympathetic and parasympathetic nervous systems
parasymp - acetylcholine
symp - adrenaline
Nerves for sympathetic split off from what part of spinal cord
cervical, thoracic (midsection), and lumbar - sympathetic ganglia
Nerves for parasympathetic split off from what part of spinal cord
brain stem and sacral regions
Forebrain
- cerebral cortex
- amygdala
- hippocampus
- basal ganglia
- thalamus
- hypothalamus
(CAH-BTH)
Midbrain: regions and the neurotransmitters produced/that dominate in that area
- raphne nucleus (serotonin)
- sustantia nigra and ventral tegmentum (dopamine)
- locus coeruleus (norepinephrine)
- periaqueductal grey (this is the pain centre, endorphins)
- reticular formation also part of midbrain
(RSVP L)
Hindbrain
- Cerebellum
- Pons
- Medulla
- Reticular formation
(CPR and medulla)
Cerberal Cortex
cortex is required for:
- consciousness
- perceiving and integrating sensory information
- storing and retrieving memories (not necessarily encoding)
- self-reflection
- planning
- decisions about voluntary behaviours
- higher though and reasoning
Basal Ganglia
- initiating voluntary movement
- reward system (pleasure)
- decision making
Thalamus
- information filter: relay between the cortex and the sun-cortical structures
- involved in consciousness
- can be a target for anti-epileptic drugs
- anesthesias also act here
Hypothalamus
- endocrine system - produces hormones
- regulates stress response
- controls hunger and satiety
- hypothalamus neurons secrete hormones into either the bloodstream or into terminals of the pituitary
Limbic System
- mediates emotional responses and memories
- includes the cingulate gyrus, basal ganglia, amygdala, and the hippocampus
- cingulate gyrus: mediates concepts of self and others, memory storage and retrieval with emotional content
- amygdala: negative emotion/ fear
- Hippocampus: memory formation and retrieval, spatial memory, autobiographical memory
Pituitary Gland
- releases hormones from secretory cells into the bloodstream
- controls other endocrine glands: adrenal, thyroid, ovaries, testes
- hormones include: gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), oxytocin, vasopressin, and orexin.
reticular formation
in the midbrain and extends down to hindbrain
- involved in sleep and attention, consciousness and habituation
cerebellum
part of hindbrain
- coordinates and refines movements and timing
- maintains balance and posture
pons
part of hindbrain
- relay point for spinal neurons and cranial nerves
- location of monoamine neurons and reticular activating system
medulla oblongata
part of hindbrain
- heart rate, respiration, blood pressure, vomiting, swallowing, sneezing
The blood brain barrier
the blood vessels of the capillaries in the brain are very tightly joined so nothing can get by (unlike leaky junctions everywhere else in body)
- epithelial cells have specialized tight junctions (TJs) and adherens junctions (AJs) that restricts the movements of molecules
how do charged or large molecules get past the BBB?
- some charged molecules are actively transported by transporters (glucose, amino acids)
- things like transferring, insulin, and leptin receptors get in by transcytosis.
What can get through the BBB no prob?
- lipophilic molecules and drugs can pass passively through the cell membrane of the BBB and into the brain (ex. steroids like estrogen)
What does the BBB exclude?
- highly charged particles and drugs
- large proteins
- bacteria
- viruses (viruses that do get in are hijacking a transporter - will cause meningitis)
- blood and plasma cells (so also keeps out immune cells them - what are implications of this)
brain regions not protected by the BBB
- pituitary gland (hormone secretion)
- pineal gland (melatonin secretion)
- area postrema (vomiting, senses blood for poisons)
What conditions can impair the BBB and its integrity?
- stroke (ischemia)
- head trauma
- inflammation
- alzheimer’s disease
- ALS (amyotrophic lateral sclerosis)
- multiple sclerosis
What feature makes it easy to exclude a drug from the brain but also difficult to develop drugs for the CNS?
Charge of the molecule
- charged molecules can’t get into the CNS
BUT
- most drugs interact with their targets by charged residues of the drugs interacting with the charged amino acids
CNS is composed of…
neurons, astrocytes, oligodendrocytes, and microglia
What do most CNS drugs target?
Neurons and their propensity to fire (not astrocytes, oligod, or microglia)
postsynaptic density
area on the postsynaptic neuron where you find receptors
classical neurotransmitters
NTs that are packaged in a synaptic vesicle
Amino Acids:
- glutamate (excitatory)
- GABA (inhib)
- glycine
- acetylcholine (mostly excitatory)
Monoamines (effect depends on GPCR their receptor is coupled to - Gs, Gi, Gq):
- dopamine (DA)
- norepinephrine/noradrenaline
- epinephrine/adrenaline
- serotonin (5HT)
- histamine
neuropeptides like endorphin and enkephalin
non-classical neurotransmitters
not packaged into vesicles, rather they are produced by enzymes and freely diffuse across cell membranes to alter local neuron physiology
- nitric oxide
- endocannabinoids
- prostaglandins
Ten spots/drug targets at which to modulate neuron function
- action potential of presynaptic neuron
- synthesis of NT
- storage of NT into vesicles
- intracellular metabolism of NT
- vesicular release of NT
- re-uptake of NT into presynaptic neuron or glia
- degradation of NT in the synaptic cleft
- binding of NT to postsynaptic receptor
- receptor-induced change in excitability
- retrograde signalling (chemicals produced in postsynaptic neuron diffuse to influence presynaptic neuron)
autoreceptors
receptors on the presynaptic terminal
- sensors to detect the synaptic levels of a NT
- normal function is to attenuate release of the NT (causes intracellular cascade that reduces NT released)
- often have a higher affinity for the NT than the postsynaptic receptor
what are the implications of giving a drug at a low-dose when an autoreceptor has a higher affinity for the NT than the postsynaptic receptor?
if the drug binds at the orthosteric site (the site where endogenous chemicals would act), the drug would bind to the autoreceptors more than the PS-receptors causing an attenuation of more release
Most psychoactive drugs are agonists or antagonists of…
neurotransmitter receptors or voltage-gated ion channels
- act to either increase or decrease the probability that a neuron will fire by directly or indirectly (activating g proteins indirectly affects ion channels) modulating ion channels
Components of resting membrane potential
- bulky anions (can’t leave.cell)
- sodium ions are kept low inside (creates conc gradient and electrostatic pressure)
- chloride ions are low inside (so will rush in even though inside is all neg)
- potassium ions at high conc inside (conc gradient)
- calcium ions are kept low in the cell (conc gradient and electrostatic pressure)
what does it take for a neuron to fire?
- NTs at the synapse cause sodium channels (ligand-gated) to open
- sodium rushes in, depolarizing the membrane
- nearby sodium channels open (voltage-gated), propagating the signal down the axon
- at the terminal, voltage-gated calcium channels allow calcium into the terminal, signalling the release of NT vesicles
