Memory Systems Flashcards
(23 cards)
what structures make up limbic system
medial temporal lobe with parts of diencephalon
hippocampus
anterior thalamic nuclei
amygdala
adjacent cortical areas (entorhinal cortex, perirhinal cortex, parahippocampal cortex)
function limbic system
memory formation and emotional processing, esp fear
hippocampus - memory function hypotheses
- hippocampus stores incoming info and acts as temporary buffer ‘consolidating’ info and will pass info on to cortex for ultimate storage
- long term memory is sorted in hippocampus which is essential for long term memory
available data supports hypothesis 1. but controversial. it is a network, deficit in any part will have an impact. doesn’t mean info is stored there, may just be needed to access info which is stored elsewhere
declarative memory
(explicit)
included episodic and semantic memory
non-declarative memory
(implicit)
habits and skills, implicit emotions
episodic memory
individual experience related to past event
e.g. wedding
semantic memory
meaning of something w/o remembering specific even where learnt it
e.g. know what a strawberry is but don’t know when learnt it
Alzheimer’s end stage pathology
beta amyloid plaques
tau tangles
enlarged ventricles
inflammation
cortical atrophy
Alzheimer’s characteristics
progressive cognitive decline
Alzheimer’s: ABC score
A: amyloid deposition
B: break stage of neurofibrillary tau tangles
C: CREAD nutrition plaque score
Alzheimer’s: genetic link
<1% cases purely genetic cause
linked to APP on Chr21 , familial mutations –> familial AD
(pt with trisomy 21 have extra chr21 –> APP on this chromosome)
Alzheimer’s: genetic risk factors
apolipoprotein E
people with one cope APOE 4 are 3x more likely to be affected by AD
AD pathophysiology: current key hypothesis
APP processing & b-amyloid plaque neurotoxicity
hyperphosphorylation of Tau
oxidative stress and ageing
diet and environmental factors (e.g. metals)
cholinergic signalling
cholinergic hypothesis
reduced levels of ChAT (enzymes which generate ACh
loss of cholinergic neurons
affects target areas of cholinergic projections –> hippocampus and cortex (which are important for learning and memory)
currently only symptomatic treatment target
formation of beta amyloid plaques
APP is transmembrane protein which is usually cleaves and produced by a growth factor - secretase APP alpha
in disease state, APP is cleaved by a different secreatase and produces beta amyloid protein which then forms plaques
formation of tau tangles
oxidative stress and free radial formation –> disregulation of specific protein kinases –> hyperphosphorylation of tau
tau then comes away from the cytoskeleton and forms the tangles
attempts to link amyloid and tau
amyloid dysregulates protein kinases –> tau hyperphosphorylation
but there is spatial paradox: tau and amyloid pathology do not start in same bits of brain
if one induces other they should start same area of brain
amyloid hypothesis
proposed amyloid as cause of AD
how does beta amyloid hypothesis not satisfy criteria for casual relationship with AD
dose response: you don’t get worse degree if more beta amyloid
temporal sequence: amyloid does not occur before see other damage
specificity: amyloid seen in other ND disease and in healthy people
toxic protein propagation through brain
specific protein for each pathology
proposes that start with BA then tau comes in, then structural damage and oxidative stress. need sensitive detection for these
AD risk factors
htn & CVS disease
sedentary, obesity, poor diet
alcohol
low levels cognitive engagement
stroke
smoking
depression
sleep disorders
metal exposure as risk factor for AD
metals can induce tau hyperphosphorylation (high number of metal binding sites in tau proteins)
metals induce higher complex amyloid fibrils
CNS metal physiology
Glut synapse - zinc co released with glutamate at high conc.
NMDA receptors have zinc binding site and depending on if this is occupied or not will have more/less calcium influx into post-synapse.
GABA receptors have metal binding sites. Will regulate excitation of nervous system - need good control over metal homeostasis
APP - number secreatases have copper and zinc binding sites which are essential for enzymes to work
beta-amyloid fragments have metal binding sites and when occupied get oligomers —> metal rich plaques
BA is cleared by enzyme which has zinc binding sites.
