Neuroscience Flashcards
7 main parts of the CNS
Spinal cord, Medulla Oblongata, Pons, Cerebellum, Midbrain, Diencephalon, Cerebrum.
What is the corpora quadrigemina?
4 hills, top bumps = Superior Colliculi. bottom bumps = Inferior Colliculis.
Located on the posterior surface of the midbrain
Where do nuclei reside?
CNS (midbrain)
Where do ganglia reside?
PNS
What is the midbrain in control of?
Motor movement and eye and auditory processing
What does the Cerebellum mediate?
Coordination, balance and muscle tone
Diencephalon components
Thalamus, Hypothalamus and pineal gland
What does the thalamus do?
Act as a switchboard to cerebral hemisphere and cortices, sends and receives signals from cortex.
Important for sleep and wakefulness, coordination of information.
How does the thalamus act as a relay?
Fibres project into thalamus, which coordinates the information and projects fibres back into the cortex.
Has links to basal ganglia and cerebellum.
How many layers of grey matter is the outer cortex?
6
What is the inner portion comprised of?
White matterr
Neocortex
6 layers, newer evolutionary part of brain, responsible for language and conscious thought
Neocortex
6 layers, newer evolutionary part of brain, responsible for language and conscious thought
Any parts with less than 6 layers
Allocortex
Allocortex sections
Subdivided into the archicortex and paleocortex
Ridges
Gyri
Grooves
Sulci
Two important ridges:
Central sulcus and lateral sulcus
Why are these ridges important?
Used to separate functionally important lobes of the brain
Occipital lobe
Vision processing region
Temporal lobe
Processing and sensory input, long term memories, emotion and language perception
Parietal lobe
Integrates sensory information including touch, spatial awareness and navigation
Frontal lobe
Decision making and planning
Main function of brainstem
Regulation of heart and breathing rate
Which part of the cortex is important for higher functions such as language and cognition?
Neocortex
Dendrites
Recieve messages from other cells
Terminal branches of axons
Form junctions with other cells
Axons
Pass messages away from the cell body to other neurons, muscles or glands
Neural impulse
Electrical signal travelling down the axon
Myelin Sheath
Covers axon of neurons to help speed neural impulses
Cell body
Cell life support
Action potentials -
Electrical signals that enable rapid signalling within neurons
Chemical communication
Way in which signals are transferred between neurons at the synapses
How are changes in membrane potentials generated?
By movement of ions across the membrane
What ion is responsible for resting potential?
K+
What ion is responsible for action potential?
Na+
How are action potentials described
As an all or nothing response - UNIDIRECTIONAL
Amino acid neurotransmitters
Glutamate, Aspartate, GABA and glycine
What is the major excitatory neurotransmitter?
Glutamate
How does Glutamate release work?
Synthesised by enzymes from glutamine –> glutamate
Packed into secretory vesicles
When synapse fuses with membrane - releases into synapse
What is the major inhibitory neurotransmitter?
GABA
Biogenic amines role
Regulate brain function, implicated in a wide range of cognitive functions
What do biogenic amines often modulate?
Effects of glutamate and GABA
Examples of Biogenic amines
Catecholamines (Dopamine, Norepinephrine and Epinephrine), Serotonin and Histamine
What do defects in biogenic amines lead to?
Most pyschiatric disorders
Dopamine role
Plays an essiential role in coordination of body movements and interaction of ventral tegmental area neurons which have central roles in reward and motivation circuits.
What is the link between
Dopamine and Parkinsons
Dopaminergic neurons of the substantia nigra degenerate, giving rise to the characteristic tremors.
Where do recreational drugs usually function?
Ventral tegmental area neurons - alter dopamine release by modulating signalling/breakdown
Serotonin role
Links to mood and the bowels
What has research shown about serotonin production
Enteric neurons can produce it in response to things happening in the gut.
Small molecule neurotransmitters examples
Acetylcholine, Glutamate, Gaba, Biogenic amines
What do all small molecule neurotransmitters have in common?
They are all produced and released quickly
Neuropeptide features
Encoded by genes
Slow life cycle
Long range action
Chain of amino acids
Life cycle of a peptide transmitter
- Transcription
- Vesicle
- Ca2+ dependent exocytosis
- Receptor binding
- Inactivation
- Diffusion
Which neurotransmitter is faster peptide or small molecule?
Small molecule
Peptide slow
Post synaptic effects of peptide neurotransmitters
Can activate at low protein concentration
Synaptic and distanced targets
Examples of neuropeptides
Orexin, Vasopressin/Oxytocin, Endorphin, somatostatin
Two classes of neurotransmitter receptors
Ligand gated ion channels - ionotropic and G-protein coupled receptors - metabotropic
How do ligand gated ion channels work?
Transmitter binding opens an ion channel, causes changes in post synaptic potential
How do G protein-coupled receptors work
Transmitter binding activates a G protein, this activates effectors which induces cellular signalling
Examples of Excitatory transmitters with gate cation channels
Acetylcholine and glutamate
Examples of inhibitory transmitters with gate anion channels
GABA, glycine
NMDA
Agonist N-methyl-D-asapartate
AMPA
Agonist alpha amino-3-hydroxy-5-methlisoxazoleproprionic acid
What are NMDA and AMPA
Types of glutamate receptor
What does AMPA mediate
Fast excitatory neurotransmission
What are the effects of agonists such as benzodiazepines and barbituates?
Drowsiness and calmness effect
What are responses to G-protein coupled receptor activation
Phosphorylation, Transcription of cAMP and activation of kinases
How are fast responses through ion channels achieved?
By Membrane potentials
How are slow synaptic responses achieved?
Phosphorylation/dephosphorylation and transcriptional regulation
How does neurotransmitter release occur?
- Action potential comes down the axon, leads to voltage gated calcium channels opening
- Ca2+ enters, causing fusion of vesicles to synaptic membrane
- NT released from Ca2+ influx, exocytosis from vesicles
What catalyses the fusion of vesicles with the plasma membrane
SNARE proteins
What are the SNARE Proteins?
Synaptotagmin and Synaptobrevin, mediate the binding of vesicles to the plasma membrane
Synaptobrevin
Syntaxin, SNAP-25 forms tight complex
Synaptotagmin
Acts as a Ca2+ sensor and triggers rapid fusion
Which part of the brain is affected in Alzheimers?
Hippocampus, important for memory storage - causes severe dementia
What is seen in autopsy patients with Alzheimers?
Atrophied brain, Ventricle enlarged, Amyloid Plaques and intracellular filaments
Brain areas affected in alzheimers
Cortex, Hippocampus, Ventricles
What are amyloid plaques
Extracellular aggregates of insoluble beta-amyloid peptides
AB42
What are intracellular filaments
Neurofibrillary tangles formed y hyperphosphorylated forms of microtubule associated protein tau.
What is the cellular pathology of Alzheimers?
- Extracellular aggregates of insoluble B-amyloid peptides
- Intracellular tau tangles
- Neuronal death
Genetic causes of Alzheimers
APP, PSEN1 and PSEN2
What does APP encode
Amyloid precursor protein
How does APP mutations lead to amyloid plaque formation
Abnormal processing of APP, leads to aggregation of excess AB42 as a result of APP cleavage.
Criticisms against the amyloid cascade hypothesis
- Plaques are present in cognitively normal individuals
- Amyloid hypothesis has so far failed clinically
What is Parkinsons
Degeneration of dopaminergic neurons in the substantia nigra
Symptoms of Parkinsons
- Slowness/absence of movement, rigidity and resting tremor
- Difficulty initiating movement
- Slow movement
- Stiff and inflexible muscles
Why do dopaminergic neurons degenerate?
Due to Lewy bodies, they are inclusion bodies that are abnormal aggregates of protein which develop inside nerve cells affected by parkinsons.
What causes Lewy Bodies?
Familial forms of PD show mutations in the gene SCNA, encodes a-synuclein.
Gut microbiome
How do aggregates form in PD?
a-synuclein misfolds, which causes other proteins to misfold until clumps form in the brain
Which techniques are used to look at microbiome composition in human samples
- 16s rRNA sequencing
- DNA sequencing –> Shotgun
- Metabolomics
- Metagenomics
Techniques used to assess causative relationship of gut microbes and brain function?
- Use of germ free mice, infect with fecal transplant
- Cut vagus nerve - route of communication lost
Examples of how gut microbes perform functions important to the host
- Extract energy from host indigestible carbohydrates
- Produce vitamins (K)
- Develop gut and systemic immunity
- Prevent pathogenic colonization
- Maintenance of the intestinal barrier
Cultivation dependent techniques of studying microbiome
- Microbiology
- Growth kinetics
- Morphology
DNA based approaches
16S rRNA, 18s, iTS gene sequencing.
What is the simplest type of sequencing
16s rRNA
Why is the 16s rNA gene used
Varies a lot between bacterial species, allows classification of bacteria present
What does Metagenomics assess?
All genes of all the bacteria, determines sequences of entire genomes via shotgun sequencing
What was seen in patients with Alzheimers disease?
Less microbiome diversity, not as many species, species richness was different
Mechanisms by which microbes can alter brain function
- Neurotransmitter, Immunity, Vagus nerve. and Bacterial Molecules.
How do microbes alter brain function through neurotransmitter?
Microbes can affect cells in a way that causes NT release, which can affect nerve cells in the enteric NS and beyond
How do microbes alter brain function through Immunity?
Immune cells in the gut respond to what is happening within the gut an
How do microbes alter brain function through the Vagus Nerve?
Connects gut to NS, pathway of communication
How do microbes alter brain function through Bacterial Molecules?
Microbes produce metabolites which can alter the activity of cells in the blood-brain barrier
How many cranial nerves are there?
12
What are the sensory functions of the vagus nerve
Coordinates sensory information from the organs in the chest and trunk
What are the motor functions of the Vagus Nerve
Stimulate muscles in organs in chest and trunk, including those in the digestive tract
What sort of receptor is NMDA
Voltage-dependent
What blocks NMDA at resting potential
Mg2+
