Pharmacology CNS Flashcards
What is the CNS composed of?
The brain and the spinal cord
What are the different regions of the brain?
Brain stem
Cerebellum
Forebrain
What are the cavities in the brain?
Called ventricles, contains the cerebrospinal fluid
What are the functions of the brain stem?
Relay centre- all info from spinal cord
Reticular formation- important in consciousness and wakefulness
Reflexes involved in balance and posture
Site of exit for most cranial nerves
What is the function of the relay centre in the brain stem?
All info from spinal cord
Information between higher brain and spinal cord
Initial processing (neural integration)- synapses, not a passive process
What is the function of reticular formation in the brain stem?
Important in consciousness and wakefulness
Network of neurones throughout the brain stem
Receives and integrates sensory input from periphery- ‘filters’ unnecessary information
Consciousness- unconscious when sleeping-only allows very important info, arousal (wakefulness)= reticular activating system
Name the different areas of the brain stem:
Midbrain (top)
Pons (middle)
Medulla oblongata (bottom)
Describe the functions of the medulla oblongata:
Involuntary functions
-vital reflex centre (control of breathing, circulation, digestion e.g the respiratory control centre)
-non vital relex centre (e.g coughing, vomiting (chemoreceptor trigger zone-CTZ, when stimulated, triggers vomiting))
Describe the function of the midbrain:
Contains the substantia nigra
Important in Parkinsons disease
What are the functions of the cerebellum?
Attached to the brainstem
involved in co-ordinated voluntary movement (fine control)
Integration of information:
-position of the body
-sensory info from muscles, joints, skin, eyes, ears, viscera, inputs from motor areas of the cerebrum
-involved in planning and initiation of movement, inputs from motor areas
-Procedural memory, co-ordination of subconscious motor tasks
Balance
Eye movement
Name the two areas of the forebrain:
Cerebrum
Diencephalon
Name the two subparts of the diencephalon:
Thalamus
Hypothalamus
What is the function of the thalamus?
Relay centre
Sensory input (all via thalamus, preliminary processing, filtering, directing of signals)- directing attention
Motor control
What is the function of the hypothalamus?
Major homeostatic control centre
Integrates homeostatic input e.g BP, HR
Regulation of autonomic NS and endocrine system
e.g control of body temp
Controls secretion of hormones by the pituitary gland
Forms part of the limbic system (emotion, behavioural patterns and memory)
Role in sleep wake cycle
What is the limbic system?
Interconnecting group of structures in the forebrain
Basic emotions
Neural centres controlling basic behaviour
Olfaction (smell)- olfactory bulb
Hippocampus (memory)
Describe the basic emotions due to the limbic system:
Fear, anxiety, anger- stimulate amygdala
Pleasure, satisfaction- septal nuclei
Describe the neural centres controlling basic behaviours in the limbic system:
Preparing for attack/ defence, laughing, crying
Survival- eating, drinking, sexual behaviour- reward pathways- drug stimulating these pathways can cause addiction
Punishment pathways
Describe the composition of the cerebrum:
Consists of the cerebral cortex and the basal nuclei (aka basal ganglia)
Collections of neuronal cell bodies (nuclei or ganglia) includes stratum (caudate nucleus, putamen and separating structure), globus plaids
Also the substantia nigra and the subthalamic nuclei in the brainstem
What is the function of the cerebrum?
Involved in control of movement (extrapyramidal motor system)
Modulation of motor activity- generally an inhibitory role
Inhibit muscle tone (stop muscle being contracted)
Purposeful vs unwanted movements
Posture/support (co-ordination of sustained contractions)
Describe the structure and function of the cerebral cortex:
Two hemispheres, left and right
80% of weight of human brain
Consists of a shell of grey and an inner mass of white matter
Highly convoluted to increase surface area
Control collateral side of body e.g left hemisphere will control movement of right side of body
Hemispheres aren’t completely symmetrical in structure nor equivalent in function
What does the grey matter consist of?
Cell bodies
Dendrites
Glia
What does white matter consist of?
Myelinated axonal tracts
Describe why the cerebral cortex is highly convoluted (folded):
Gyri (gyrus)= peaks
Sulci (sulcus)= troughs
Increases SA of grey area so increased processing, amount of convolution is proportional to the complexity of the organism
What is the function of the cerebral cortex?
Concerned with ‘higher functions’ including sensory analysis and perception, conscious though, language, motor initiation (voluntary) and co-oridination, intullect
Name the different lobes of the brain:
Frontal lobe
Parietal lobe
Occipital lobe
Temporal lobe
Describe the features of the frontal lobe:
1º motor cortex
Premotor area
Prefrontal area
Separated by the lateral and central sulcus
Has the Broca’s area
Describe the features of the parietal lobe:
1º somatosensory cortex
Somatic sensory association area
Has the Wernicke’s area
Describe the features of the occipital lobe:
1º visual cortex
2º association area
Describe the features of the temporal lobe:
1º auditory cortex
2º association area
Describe the somatosensory cortex:
Analyses inputs from mechanoreceptors (touch, stretch), thermo receptors and nociceptors (pain) in the skin, muscles, joints and internal organs
All the information goes via brain stem to the thalamus to the somatosensory cortex which receives info from receptors on the opposite side of the body
Where is the somatosensory cortex located?
Parietal lobe of the cerebral cortex
What is somatotrophic organisation?
Increase size of brain where the brain area is devoted to a particular part of the body means increased pain e.g hands/ lips occupy greater area of brain so more pain
The area of cortex devoted to each area is proportional to the amount of info received from that area
What is ‘plasticity’ in somatotrophic organisation?
There is ‘plasticity’ within the neurons of the somatosensory cortex (if one area received extra stimulation or decreased stim the size of the devoted area will change accordingly)
Where does information go once it reaches the somatosensory cortex?
Information passes to its ‘association areas’ where further processing occurs, before combining with other sensory input and then information form past experiences
-analysis, integration, perception
What is the motor homunculus?
Use dependency for cortical space
Plasticity- more an area is used, the more cortex will be devoted to it
Describe the motor control in the motor cortex:
Responsible for voluntary movements
Motor cortex sends signals to the a-motor neurons
Motor cortex has input from the supplementary motor area, premotor cortex, posterior parietal cortex, basal ganglia, thalamus and cerebellum
-planning, programming, co-ordination of complex movement
What are the areas involved in motor control?
Pre-motor cortex
Supplemental motor area
Describe the cortical areas involved in language:
In 90% of people, the left hemisphere is used in relation to language
Distinct areas are specialised for the production and understanding of language
Aphasias (language deficits resulting from brain damage) have enabled the language centres to be identified
Broca’s area
Wernicke’s area
What is the function of Broca’s area?
Involves the articulation of speech (controls muscles via motor cortex for speaking)
Damage= understand language but can’t speak
What is the function of Wernicke’s area?
Involves comprehension and planning/coherence of language
Damage= struggle to understand what has been said and words coming out the wrong way- even hearing and reading words
Somatosensory for braile
Name the 4 different glial cell types:
Astrocytes
Microglia
Oligodendrocyte
Ependymal cells
What are the role of the astrocytes?
The most abundant glial cells in the CNS- even more than neurons
Dynamic role
Structural support
BBB
Repair- scar tissue (glial scar)
*Maintance of the extracellular environment
Modulation of synapse function
How does the astrocyte have a dynamic role?
Communicate with each other (gap junctions and chemical signals-neurotransmitters) and with neurones
How is the astrocyte involved in structural support?
Including scaffold development- guide developing axons to the right place
How is the astrocyte involved in the BBB?
Foot processes, contract BVs of CNS
How is the astrocyte involved in the maintenance of the extracellular environment?
Needs to be kept constant for neurone function
Neurotransmitters (astrocytes remove neurotransmitter (NT) from EC fluid to presynaptic terminal)
Keeps K+ conc low- if K+ increases, neurons will depolarise ands stop them from working properly
Astrocytes have transporters on membrane so can take NTs into cell, breakdown NT and store precursor, return precursor back to neuronal cell
How is the astrocyte involved in the modulation of synapse function?
Formation
Maintenance
Modification of NT release
What is the function of the microglia?
Immune cells of the CNS
Macrophages of the CNS
-scavengers
-release of cytokines
Role in neurodegenerative disease
Name and describe the different forms of microglia:
Resting or activated - structural differences
Resting (look thin/sparse), homeostatic
Activated (thicker- retract- less ramified- amoeboid):
-mobile- can move to damage in CNS tissue
-pro inflammatory if cytokine response not well controlled
What is the function of the oligodendrocytes?
Form the myelin sheath around neuronal axons
White matter
What is the function of ependymal cells?
Epithelial cells
-lines the fluid filled cavities of the CNS (ventricles)
Secrete cerebrospinal fluid (CSF)
Ciliated- important in moving the CSF with the ventricles
BBB
Name the 9 neurotransmitters:
Acetylcholine, Noradrenaline, Adrenaline, Dopamine, Serotonin (5-HT), Histamine, Glutamate, GABA, Glycine
Which neurotransmitters are catecholamine neurotransmitters?
Noradrenaline, adrenaline and dopamine
Which neurotransmitters are amino acid neurotransmitters?
GABA, glutamate and glycine
How is glutamate synthesised?
Can be synthesised in the presynaptic terminal
From glucose (via TCA cycle) GABA-T enzyme
From glutamine by action of glutaminase enzyme
What is glutamate?
A universal cellular constituent and a non-essential a.a
What are the 2 major cellular sources of glutamate?
Metabolic glutamate
Transmittable glutamate
Name the two types of glutamate receptors:
Metabotropic glutamate receptors (mGluRs)
Ionotropic glutamate receptors
Describe the ionotropic glutamate receptors and their different classes?
Ligand gated ion channels
NMDAr
AMPAr
Kainate r
What are the differences and similarities between the 3 classes of ionotrophic glutamate receptors?
They 3 classes are separated on responsiveness to synthetic analogues
NMDAr only responds to NMDA
All activated by L-glutamate
Different pharmacological properties
Different biophysical properties and functional effects on neurones
All have similar structures, tetramers- 4 subunits
Describe the NMDA receptors:
Assembles from 7 potential subunits encoded by 7 different genes
GluN1, GluN2A, GluN2C, GluN2D, GluN3A, GluN3D
The receptor is a tetrameric complex- hetero tetramer (mixture of subunits)
Typically 2 GluN1 and 2 GluN2 subunits come together
Alternative splicing can affect the GluN1 gene (8 variants identified)
Describe the structure of the NMDAr:
Each subunit of the tetramer has:
-extracellular N-terminal domain labelled ATD (amino terminal domain
-an extracellular ligand-binding domain (LBD)- binds the agonist
-three transmembrane spanning a-helical domains (M1,M3,M4)- hold ion channel in plasma membrane
One re-enterent P-loop called M2
An intracellular C-terminus
What properties can the NMDAr composition affect?
Agonist and co-agonist potency
Deactivation rate- how long the ion channels stay open for
Mg
Ion permeation (e.g pH)
Channel conductance- how ions move through channel
GluN2 subunits affects pharmacology of NMDAr
What are the ion channel responses for AMPAr and kainite receptors?
Desensitisation occurs rapidly- rapid activation and deactivation
What are the ion channel responses for NMDAr?
The extent and time- course of destination of the NMDAr depends on the subunit
Cation selective ion channel, Na+, K+, Ca2+
Noted for its high permeability for Ca2+ ions
GluN2A/B deactivating rapidly
GluN2C/D deactivating slowly
Name the binding sites for the NMDAr:
Glutamate (agonist site) or receptor site
Glycine site
Polyamine binding site
Mg2+ site
Channel blocking site
Describe the agonist activation of the NMDAr:
Each tetramer binds two molecules of glutamate
EC50 value for glutamate is 0.5-3µm (dictated by GluN2 subunit)
NMDA is a synthetic agonist- works the same way as glutamate
Describe the co-agonist activation of the NMDAr:
2 molecules of glycine are required for full activation
EC50 value 1µm
D-sereine, D-alanine can also act as a co-agonist
GluN1 is the glycine binding site