1) Neuroplasticity Flashcards
Neuroplasticity (definition)
= ability of the brain to reorganise its structure and function due to intrinsic or environmental demands by weakening and strengthening of pre-existing synaptic connections and the formation of new synapses
- changes can be: chemical, structural, functional –> axonal growth, neurogenesis (in hippocampus)
- influenced by: aging, degeneration, malnutrition, environment, lesion/pathology induced, cognitive and physical exercise, etc.
- plays a role a role in almost every neuropsychological disorder –> depression, schizophrenia, etc.
Benefits and disadvantages of neuroplasticity
High plasticity
- weakly connected network –> high susceptibility to change the state of the system
- changes easily between pathological and healthy sates –> more susceptible to change to pathologcial state BUT also easier to change back to healthy state
- in a favourable environment: promotes wellbeing
- in unfavourable environment: increases vulnerability
Low plasticity
- strongly connected network –> low susceptibility to change the state of the system
- more difficult to change system between healthy and pathological states –> less susceptible to change from healthy to pathological BUT also more difficult to change from pathological to healthy state
- in favourable envionment: slows down improvment
- in unfavourable environment: prevents worsening
Neurogenesis
= growth of new neurons
- previously thought to occur only during development
- post-mortem: signs of neurogenesis in hippocampus
- corroborated in adult mammalian brain in various species and also found in the subventricular zone of the lateral ventricles
–> network reorganisation, connectivity
Synaptic plasticity
= experience-based change in connectivity between neurons that is believed to underlie learning and memory
Complex mechanisms
- modulation of transmitter release
- trans-synaptic signalling
- post-synaptic receptor dynamics
- gene expression within neurons
- well-studied model for synaptic plasticity: rodent hippocampus
> long-term potentiation
> long-term depression
–> functional remapping
Hebbian learning
= connections grow in strength when amplified: ‘neurons that fire together, wire together’
- repetitive input -> positive reinforcement -> positive feedback
- LTP
- LTD
Long-term potentiation (LTP)
= persistent strengthening of synapses based on recent firing patterns
- dependent on neurotransmitter glutamate
- glutamate receptors: NMDA, AMPA
Rabbit hippocampus
- stimulation of pre-synaptic fibres lead to excitatory postsynaptic potential in dentate gyrus (expected)
- enhanced post-synaptic response due to high-frequency stimulation: tetanus (unexpected)
Long-term depression (LTD)
= activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus
- synaptic weakening to make effective use of LTP: otherwise ceiling effect (all synpases become stronger and stronger)
Synaptic scaling: Homeostatic (synaptic) plasticity
= fine tuning at the level of the whole neuron or dendritic branches (= non-Hebbian plasticity)
- aims for equilibrium
- introduces dampening of negative feedback into a neuronal network
- changes in intracellular Ca2+ associated with synaptic scaling
- Calcineurin (Ca2+ sensor) block synaptic scaling
- local retinoic acid (RA) gradients required for homeostatic synaptic plasticity -> inhibits local AMPA translation
- RA signalling is increased when synaptic activity or Calcineurin are inhibited -> blocked by RA synthesis (inhibitor DEAB)
- inhibition of Calcineurin OR addition of RA result in increased synaptic strength
- homeostatic synaptic plasticity requires presence of RARa, Calcineurin (CaN)
Hebbian plasticity vs homeostatic plasticity
Hebbian
= plasticity though selective strengthening/weakening of specific synapses based on their activity
- strength of synaptic connections is based on their activity (LTD/LTP)
- information encoding (function)
PROBLEM:
- uncontrolled positive feedback (LTP)
> harmful excitation could form instabel neuron circuits
> could limit the neurons range of adaptability
Homeostatic
= all neuronal changes that tend to return the neuron back towards an initial set point
- synaptic scaling = global adjustemt of all synaptic inputs to a neuron in response to prolonged changes in activity without altering the relative differences between synapses
History: 1890 - William James
plasticity in the wide sense of the word
- possession of a structure weak enough to yield to an influence, but strong enough to not yield all at once
- relatively stable phase of equilibrium in such a structure is marked by what we may call a new set of habits
History: 1904: Ramon y Cajal
- in adults, the nerve paths are something fixed, ended, immutable
- everything may die, nothing may be regenerated
- science of the future needs to change that if possible
Used Golgi stain and concluded
- neurons are single, yet connected entities
- non-self repairing tissue
Golgi: Reticular theory
- hard-wired, connected like vessels
Ramon y Cajal was right
Types of cells in the brain
three important types of cells in the brain
- neurons = transmission of action potential
- glia = connective tissue
- microglia = immune cells of the brain, similar to macrophages
–> do not exchange too much with periphery
–> generated by monocytes (type of white blood cell) in blood
- very important role in plasticity –> prune synaptic connections (‘eat synapses’)
Drivers of neuroplastic changes
1. Diet
- via blood
- Neurons: AcAc, BHB, Insulin, Glucose
2. Exercise (+Learning)
- playing sports/instrument
- in jugglers: increase in grey matter denisty
- mid-temporal area (V5) bilaterally
- left intraparietal sulcus
3. Depression
- reduction of spines (synapse)
- precise mechanism unknown: treated state more spines
- anti-depressants influence neurotransmitters
4. Drugs
- influence neurotransmitter systems
- coffeine, nicotine, ketamine –> influence on gluterminergic system
Ketamine
- excites and inhibits certain cells
–> not clean drug: interacts with many different transmitter systems
–> unknown which interaction is responsible for which behaviour
5. Lesion-induced plasticity
- spontaneous phenonema of brain plasticity in response to damage
- destruction of neural networks stimulates a reorganisation of connections
- mechanisms still incompletely understood but seem to include:
> topographical map reorganisation
> functional remapping (esp. peri-lesion areas)
> sprouting of new fibres and unmasking of existing ones
> modulation of neurotransmitter balance
- functional and metabolic changes are also observed in contralateral hemisphere
- alteration of inter-hemispheric functional connectivity
- changes may be transient (temporal dynamics)
Brain stimulation
non-invasive
tCDS = transcranial direct stimulation
TMS = transcranial magnetic stimulation
convulsive
ECT = electroconvulsive therapy
MST = magnetic seizure therapy
neurosurgical/invasive
VNS = vagal nerve stimulation
DBS = deep brain stimulation
TMS
- diagnostic procedure/neurological diagnostics
–> activate/deactivate certain cortical regions
tDCS
- 9V battery and two electrodes needed –> placed across brain
- establishes current and voltage drop
- cathodal: reduces spontaneous activity
- anodal: increase resting brain potential
- PH changes observed in brain of dead pigs
- studies need to be well blinded due to tingling effects –> at first both groups ‘receive’ treatment until tingling sensation stops –> then start experiment
ECT
- induces seizure to trigger homeostatic mechanisms –> helps brain to reorganise
- used in treatment of depression, schizophrenia, seizures
- seizure threshold drops after 6-9 treatments
Research on human brain tissue
- after neurosurgical procedure (for epilepsy) –> brain tissue left
- can be used for experiments
- BUT is not healthy - brain tissue grown from stem cells (in vitro)
- can be grown in lab, no need for surgery
- BUT are they exactly like normal brain tissue?
Electricity, plasticity, behaviour and treatment: Electrical and emotional regulation
tDCS study:
1. Anodal right dlPFC
- augments effects on arousal and skin conductance
- significant differences (increase negative emotion, reduce negative emotion) observed on skin conductance and arousal
- no difference in looking paradigm
- Cathodal left dlPFC
- faster reaction times in angry -> neutral and neutral -> angry - Anodal left dlPFC
- better cognitive control
Electricity, plasticity, behaviour and treatment: Electricity and depression
tDCS:
- can influence depression starting with first treatment
- stronger effect than anti-depressants
- after multiple session around same effect as anti-depressants
BUT translation is difficult
- 6-week CBT group intervention augmented by tDCS was not found superior to CBT plus sham-tDCS or CBT alone
