Neuroplasticity and Memory

Understand how repeated synapse use leads to changes in synaptic strength:
- This is the fundamental basis for development and memory formation.
Understand how neuroplasticity forms the basis of functional repair after brain injury.

Infants are born with 100-200 billion neurons but have very few synaptic connections.
At birth, the number of synapses per neuron is approximately 2,500.
By age 2, this increases to approximately 15,000 synapses per neuron.
The adult brain contains approximately 100 billion neurons connected by over a trillion synapses, which are used for information transmission and storage.
Experiences shape us throughout our lives, changing our behavior, perception, and thinking.
These changes are due to physical changes in the connections between neurons, such as:
- Forming new connections.
- Removing existing connections.
- Strengthening or weakening existing connections.
This occurs through synaptic plasticity.
Synaptic plasticity plays a crucial role in experiential learning and the formation of new memories.

Memory: the retention of learned information.
- Easy to form, easy to forget.
- Harder to learn, requires repetition, hard to forget.
Learning: the acquisition of new information.

The hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal cortex, are all related to the temporal lobe and memory.

Memory was demonstrated by a patient known as "H.M."
- H.M.'s brain lesion involved bilateral removal of the medial temporal lobe of 8 cm.
- This resulted in partial retrograde and extreme anterograde amnesia for long-term factual ("declarative") memories.
- Declarative memory is memory for facts and events, involving conscious recollection.

The tri-synaptic circuit involves the following pathway:
- Perforant path to Dentate gyrus (1).
- Mossy fiber from Dentate gyrus to CA3 cell (2).
- Schaffer collateral from CA3 cell to CA1 cell (3).

Hebb's Law (Donald Hebb, Canadian Psychologist):
- When a neuron persistently activates another nearby neuron, the connection between the two cells becomes stronger.
- Neurons that fire together, wire together, and neurons that fire apart, wire apart.
When neurons wire together, there is an increase in voltage change at the post-synaptic neuron with each incoming pre-synaptic signal, a process known as long-term potentiation.
High-frequency signals (strong experience) and repeated activity (studying/revising) can facilitate this process.

Induction involves glutamate, $Mg^{2+}$ , NMDA-R, AMPA-R, $Ca^{2+}$ , CaM, and CaMKII.
Postsynaptic changes encompass both receptor activity and receptor number.

Glutamate is released from presynaptic neurons (Pre-SN) onto AMPA and NMDA receptors on the post-synaptic neuron (Post-SN).
If the glutamate release is large enough (due to increased firing of Pre-SN), this will activate AMPA receptors to increase $Na^+$ influx and depolarize Post-SN, which in turn removes the $Mg^{2+}$ blockage of NMDA receptors, allowing them to let large amounts of $Ca^{2+}$ into the cell.
Increased $Ca^{2+}$ activates protein kinases that increase the trafficking of AMPA receptors to the membrane and increases the sensitivity of AMPA receptors to Glutamate.
Increased AMPA expression and activity cause larger and longer excitatory post-synaptic potentials to a given pre-synaptic input.

Anterior cerebral artery, middle cerebral artery, and posterior cerebral artery.
Specific areas of the brain are associated with different body parts.

There is a time-limited window of neuroplasticity that occurs in the brain after stroke.
Improvements in sensory and motor function over time are referred to as recovery.
Many of the molecular mechanisms that underlie stroke recovery are identical to those in development (i.e., neurogenesis and synaptic plasticity).

In the healthy control, fist closure activity is strongly lateralized to the left hemisphere with movements of the right hand.
Fist closures with the paretic hand in stroke patients were associated with enhanced and more extended neural activity, particularly in the intact cortex adjacent to the stroke lesion.

GluR1 (Glutamate Receptor Subunit 1)
Dendritic spines: thin, uncertain, mushroom, and degeneration.
New axons are regrown.
Results from an experiment
- Sham: expression of GluR1, neuronal death.
- Stroke +Saline: reduction of GluR1, Neurotrace is shown.
- Stroke +rhGH: regrowth of GluR1 in mushroom spines, new axons in infarct cavity.

Neurogenesis occurs during embryonic development and in parts of the adult brain following birth.
Adult neurogenesis is known to occur in the dentate gyrus of the hippocampus and the subventricular zone in the healthy brain and can also be stimulated after stroke.