Intro to Neurosci Flashcards
list types of neuroscience: (5)
- cognitive
- behavioural
- systems
- cellular
- molecular
define cognitive neuro:
understanding higher level (human) thought processing
define behavioural neuro:
biopsych, why/ how we produce certain behaviours
define systems neuro:
how brain controls body systems, how body systems provide info to brain
define cellular neuro:
how neurons/ glia work, signalling in cells
define molecular neuro:
how molecules/ chemicals work in brain cells to communicate, grow, change
animal welfare and ethics: proposal
- proposal approved by Animal ethics committee under NHMRC (national health and medical research council)
animal welfare and ethics: use of animals
- only for worthwhile new experiments to advance understanding
- pain/ distress minimal
- all possible alternatives considered
- research follows Aus code for Responsible conduct of research
cognitive neurosci eg:
- hippocampus, amygdala
- use of drugs trigger brain activity on PET, MRI
behavioural neurosci: list eg (3)
- elevated plus maze (rats tested to see time spent in open/ closed arms)
- anxiety
- drug use
systems neurosci eg:
- modify brain systems inject chemicals into certain brain areas
- how it effects behaviour, BP, respiration etc.
- done on freely moving/ anaesthetised animals
cellular neurosci eg:
- immunohistochemistry (staining cell types)
- electrophysiology
- connectome
- neural signalling w computer tech
molecular neurosci eg: (4)
- proteomics
- immunohistochem
- neuroinflammatory markers
- epigenetics
epigenetics: define
- functional morphology: causal mechanisms which genes/ genotype bring phenotypic effects
- molecular def: heritable changes in gene function not explained by changes in DNA sequence
- molecular mechanisms that regulate and coordinate expression of genome
epigenetics: genome model interaction w env
- og: env + genes –> influence behaviour
- now: env stimuli –> neuronal gene expression (incl epigenetic mechanisms) –> behaviour
epigenetics: why does it matter?
- involved in 30+ human neurodev disorders
- memory extinction involves epigenetic changes
- Alzheimers
- drug abuse, addiction
epigenetics: central concept of DNA
transcription - RNA processing - translation to become polypeptide
epigenetics: DNA comprises of
- packaged around histone proteins
- DNA + protein = chromatin
- tightness influences accessibility of DNA sequence to transcription enzymes
epigenetics: DNA transcription
- RNA polymerase unwinds helix, paired to RNA nucleotides
epigenetics: pattern of gene expression will?
- determines cell fate in dev, and ongoing cell function
epigenetics: mechanisms- histone modification
- changes how tight DNA sticks to histone proteins
epigenetics: general method- DNA methylation
- sticking methyl groups onto DNA chain
histone modification: how histone + DNA bind
- basic and +ve charged binding w acidic -ve DNA
- chemical mod change charge of histone
histone modification: classes of mod (4)
- acetylation
- methylation
- ubiquitinisation
- phosphorylation
histone modification: de/ACETYLation
- add acetyl gorups to lysine aa within histone
- neutralises +ve charge
- exposes DNA
- via histone acetyltransferases (HATs)
- deacetylation: increase charge
- via histone deacetylase (HDACs)
- reduces likelihood of transcription
histone modification: METHYLation HMT, HDM effects
- add (HMT)
- remove (HDM) methyl groups to lysine residues
- depends may enhance/ silence transcription
histone modification: METHYLation DNA ladder mechanism and effect
- cytosine bases methylated = 5mC
- DNMTs (DNA methyltransferase) add methyl to C/G in DNA
- reduces transcription
- maintenance DNMTs restore methyl groups after DNA replication
histone modification: DNA METHYLation + deACETYLation how does it inhibit/reduce gene transcription? (*attraction)
- physically interfere w binding RNA polymerase = inhibits transcription
- methylated DNA attracts methyl DNA binding protein - adaptor protein - attract HDACs (histone deacetylase enzymes)
- deacetylate histones increase binding histones to DNA
- methylation usually reduces gene transcription (silences gene)
histone modification: DNA de-METHYLation- Tet1 and DNMT effect summary
- Tet1 (10-11 translocation methyl cytosine dioxygenase 1)
- increase transcription
- own stable epigenetic mark
- DNMT reduces trans
- focused on gene regulatory regions (promotor programming)
neuroepigenetics:
epigenetic sys as regulators of neuronal function, influence output of neuronal circuits
epigenetics: long term memory (LTM) hypothesis
- LTM storage neurons must lock parameters so circuits stable output
- epigenetic changes provide mechanism to lock stable patterns of gene expression = stabilise functional properties of cell
Alzheimer’s disease: features
- neurodegeneration (selective death of Ach cells)
- slowly progressing dementia
- memory loss
- change in personality
Alzheimer’s disease: apraxia
loss ability to coordinate movements
Alzheimer’s disease: aphasia
loss ability to articulate ideas/ comprehend written/ spoken word
Alzheimer’s disease: agnosia
can’t interpret sensory stimuli
Alzheimer’s disease: protein and eg.
- protein accumulation in/ around neurons
- intracellular neurofibrillary tangles (NFT)
- extracellular amyloid plaques (ß amyloid protein)
Alzheimer’s disease: APP features
- amyloid precursor protein
- when cleaved (via secretases) to make secretory products in learning/ memory storage
- OR ß amyloid plaques
= hypomethylation of APP in AD
Alzheimer’s disease: tangles and plaques
- amyloid plaques before NF tangles
- APP balance shifted (genetic, env?)
Alzheimer’s disease: NFT features contd
- abnormal cluster of hyperphosphorylated tau protein
- tau usually helps maintain axon shape, transport molecules from cell body –> terminals (microtubules)
Alzheimer’s disease: genetic
early onset (50s-60s) 15% is genetic - hereditary mutations of APP processing (Aß42)
late onset (65-85yo)
- apoE gene (predispose plaque deposits),
- A2M (clears deposits, but mutates form doesn’t)
- more dependant on env
Alzheimer’s disease: list env factors (6)
- nutrition (deficient Vit B, folate)
- exposure metals, pesticides
- stress
- social factors (loss partner)
- vascular risk factors (hypertension, diabetes)
- brain trauma
Alzheimer’s disease: chemical changes seen in post mortem brain (3)
multiple changes:
- histone modification
- DNA methylation state
- causal vs consequential
Alzheimer’s disease: mouse model
- CDK5 (cyclin-dependant kinase-5) mouse
- neuron loss ß Amyloid accumulation and Tau pathology, memory loss
- increased HDAC2 at promoters vital for synaptic plasticity, memory (incl BDNF)
- reduce HDAC2 expression reversed memory impairment
Alzheimer’s disease: mostly product of
- gene x env (epigenetic) interactions
RNA polymerase: function (3)
- id promotors of gene
- signal where the gene starts
- signal when to start transcription
relo btw: 5-methylcytosine, 5-hydroxymethylcytosine, Tet1
Tet1: converts 5-methylcytosine into 5-hydroxymethylcytosine (5HmC)
- promotes transcription
ßamyloid for learning/ memory storage: % in normal vs AD
- normal: 90%
- AD: 40%
