Brain communication & plasticity

Generation of post-synaptic potentials

• Neurotransmitters in synaptic cleft bind to receptors on postsynaptic membrane and open channels

• Open channel= sodium (+), potassium (-), chloride (-) or calcium (+) ions to enter

• Changes the degree of positive or negative charge

• Excitatory or inhibitory ions 

• Change is graded 

Effect of positive ions

• increase the likelihood of a signal

• excitatory 

• depolarise the neuron to 67mV

Effect of negative ions

• decrease likelihood of a signal 

• inhibitory 

• hyperpolarising the neuron to 72mV

Conduction of postsynaptic potentials

• passive

• rapid-instantaneous

• decremental- get smaller as they travel

The net effect

(balance of + & -) determines firing of AP

Threshold of excitation

-55mV

Spatial summation

• integrating incoming signals over space

  • Location of signals is important

Temporal summation

• integrating incoming signals over time

• If fires twice quickly, will 'go off the shoulder' of the previous which will be stronger

• Determines overall response of PSN

Generation of action potentials

• If the post-synaptic potential surpasses the threshold of excitation at axon hillock

• Membrane potential is reversed from negative to positive (+30) in 1ms

• Depolarisation: Na+ (sodium) channels open = influx of Na+ into cell.

• Peak: Na+ channels begin to close, K+ (potassium) channels open.

• Repolarization: Na+ stops entering cell, K+ ions move out.

• Hyperpolarization: K+ channels start to close but some K+ ions continue to move out of cell.

Refractory period 

• follows an AP

• Responsible for:

  • Direction of travel (soma to axon)- to prevent backwards

  • Rate of firing (strength of stimulus)

Absolute refractory period:

Brief period when it is impossible to generate an action potential

Relative refractory period

Inhibited so higher than normal levels of stimulation required to generate an action potential

Conduction of action potentials

• Propagation

  • AP depolarise the axon as it travels along 

  • Non-decremental-  maintains size

  • Occurs due to influx of sodium

• Myelinated axon so AP travels faster

• Saltatory conduction: increases speed of signalling in myelinated axons

Neurotransmitter release

• When AP reaches the dendrites of the neuron

Small molecule types

few components (amino acids)

Large molecule types

contain 3-36 amino acids

• Peptides or 'neuropeptides'

• 100+ identified

• Categorised into functional groups (pituitary, opioids or brain-gut)

Amino acids & examples

• Short-chain molecules which come together to make peptides

• GABA

• Glutamate

• Monoamines- Singular components:

  • Catecholamines-Dopamine (5 types), Norepinephrine, Epinephrine

  • Indolamines- Serotonin- 5-HT, 14 types

 

Modulatory

can have both excitatory and inhibitory effects, based on receptors or location

Major dopaminergic pathways 

• nigrostriatral 

• mesolimbic 

• mesocortical 

• tuberoinfundibular tract 

Major serotonergic pathways

• Dorsal Raphe Nuclei to cortex, striatum

• Medial Raphe Nuclei to cortex, hippocampus

• Roles: mood, eating, sleep, dreaming, arousal, pain & aggression

How is a neurotransmitter produced

• Synthesised in the cell body or terminals.

• Packaged into ‘vesicles’

• Released into synaptic cleft

• Release-ready pool vesicles- Docked against the inside of the pre-synaptic membrane

How is a neurotransmitter released

• ‘exocytosis’

• AP reaches terminal of neuron

• Calcium ions enter

• Vesicles nearest to the membrane fuse with membrane

• Large neurotransmitters are released (slower than small)

Fischer's lock & key hypothesis:

• Receptors on postsynaptic membrane will only accept particular neurotransmitters

• Therefore neurotransmitters can only affect specific neurones

• Anything that binds to a receptor is called a ligand

• Therefore any neurotransmitter is a ligand of its receptor

Receptor subtypes 

• Can vary in location and response

  • e.g. Dopaminergic receptors  - D1, D2, D3, D4, D5

• Certain areas of the brain may have more subtypes than others e.g. parts of the brain will have a lot of D1, others D5

Ionotropic receptor

• Direct method

• Associated with ligand-gated ion channel

Metabotropic receptor

• indirect method

• more common

• slower response

• more varied

How is a signal terminated 

• reuptake- neurons reabsorb, back into vesicles

• enzymatic degradation- enzyme breaks up neurotransmitter into component parts so it can no longer activate receptors

Autoreceptors 

• receptors located on the presynaptic neurone in membrane

• Bind to neurone's own neurotransmitter

• DO NOT control ion channels

• Always metabotropic

• Control internal processes Incl. synthesis and release of neurotransmitters

Agonist drugs

drug mimics ligand, binding to receptor

Antagonist drug

drug blocks receptors/changes neurotransmitter to inactive

What is brain plasticity 

changes in the micro (cellular) and macro (global) structures of the brain from alterations in neural pathways & synapses

Historical perspective of brain plasticity

Until 1970s: brain structure remained relatively immutable after a critical period of development in childhood

William James

believed brain functions are NOT fixed throughout life

Donald Hebb (Hebbian theory)

postulated that brain structure could be adapted as a result of its function

• “Neurons that fire together, wire together. Those out of sync fail to link”

• Refers to systems as well as cells

Mechanisms of brain plasticity

• Brain development

• Degeneration

• Brain or body injury

• Learning (functional demand)

number of axons/ synapses in foetal brain

• 30-60% more axons than adults

• At birth 2500 synapses per neuron

• Young children have 15,000 synapses

Synaptic pruning

those that a frequently used are strong (reinforced) whilst those rarely used are eliminated

Synaptic sprouting

• After cell death keeps healthy cells involved

• New synapses require growth of new pathways

• Glial cells: provide 'scaffolding' to promote formation of new synapses

Synaptic plasticity 

• changes in the strengths of connections between synapses

  • Long-term potentiation (LTP)

  • Long-term depression (LTD)

• Activity leads to changes in synaptic transmission to potentiate or depress the synapse

  • Alter number of receptors in membranes and number of vesicles active

  • Changes in which proteins are expressed inside the cell

Maguire et al

• Demonstrates positives of brain plasticity

• Experienced taxi drivers found to have larger hippocampi than novices and controls.

• Area associated with memory  

• Grew as they spent more time in the job

• Shrunk when they retired

Gaser & Schlaug (2003)

• Expert pianists have increased grey matter density in somatomotor (where receive info from fingers) and auditory cortices

• Increased corpus callosum volume

  • Support fast transmission of info between hemispheres

  • More so for those who learnt before age 7

Pascual-Leone et al (1993) Braille readers

• Mapped motor cortex representations of reading finger using EEG and electrical stimulation.

• Cortical representation of reading finger is significantly enlarged at the expense of representation of other fingers in Braille readers

• Can even observe changes within a day when Braille is practiced for 4-6 hours

Clinical implications of brain plasticity

• phantom limbs

• stroke

Phantom limbs 

• Form of maladaptive plasticity 

• A phenomena experiences by people who have undergone limb amputations

• Associated with severe chronic pain (90%)

• Stems from the within the CNS (difficult to treat)

• Possibly a result of extreme plastic changes post-amputation.

• 'Central sensitisation'- prolonged activation of pain pathways causes system to become overly sensitive & hyperactive 

Mirror box therapy 

• Treatment for phantom limbs

• see a reflection of good hand where 'bad' hand would be and produce movements

• receives visual feedback that the absent limb is now moving

• undoes some of the maladaptive neuroplastic changes and result in pain relief.

Stroke

•  blockage causes reduced blood supply which results in cell death in a part of the brain – ‘lesion’.

• A lesion will block neuronal pathways resulting in functional deficits.

• Symptoms depend on function relevant to the area- incl. muscle weakness, apraxia, dysarthria, aphasias & cognitive deficits

• Secondary neural pathways become 'unmasked' to send neuronal signal around the blockage (sprouting)

Taub et al (1993)

Studied patients with strokes leading to poor function of one upper limb.

• Discourage patients from using their good limb

• Found significant improvement in motor function after 2 weeks lasting up to two years

Constraint-induced movement therapy:

• method for treating patients after stroke 

• Restrain the unaffected limb and promote intensive use of the affected limb.

  • Types: sling, triangular bandage, splint, mitt

  • Found that receiving CIMT early (3-9 months post-stroke) results in greater functional gains than receiving delayed treatment (15-21 months post-stroke).

  • Promotes adaptive plasticity in the affected brain hemisphere