What is Plasticity? How experience (stimulus) cause changes in the organization of the brain. Term was coined by Polish neuroscientist Jerzy Konorski 1. student of Pavlov 2. pre-eminent pioneer of the study of instrumental conditioning 3. also recognized as fathering the “grandmother-cell” concept

What is Plasticity? Plasticity relates to learning 1. learning: a. adding strength to circuits b. adding connections c. removing connections d. adding new cells to create new circuits 2. plasticity adds/removes connections - also can add new cells

What is Plasticity? Thinking, learning, and acting actually change both the brain's physical structure (anatomy) and functional organization (physiology) from top to bottom.

Recent History Lower brain and neocortical areas considered aplastic in adults 1. learning only occurs by changing connection strength 2. memory occurs in the few plastic areas left in adults a. hippocampus b. dentate gyrus

Recent History Lower brain and neocortical areas considered aplastic in adults 1. learning only occurs by changing connection strength 2. memory occurs in the few plastic areas left in adults a. hippocampus b. dentate gyrus c. new neurons produced by stem cells in these areas

Recent History Hubel and Wiesel (60’s and 70’s) 1. Ocular dominance columns in the lowest neocortical visual area were largely permanent after the “critical period” of development.

Recent History Hubel and Wiesel 2. Suturing shut a kitten’s eye during critical period resulted in failure to develop pathways for binocular vision. 3. Columns in the primary visual cortex receiving inputs from the open eye took over the areas that would normally receive input from the sutured eye. (Illustration from Hubel & Wiesel, 1979)

Recent History Hubel and Wiesel 4. kittens: 3-14 weeks 5. humans: maybe through age 5 years

Recent History Hubel and Wiesel 6. Children born with impairment in one eye (i.e, cataract) will lose vision in that eye permanently if not treated. 7. Better to keep both eyes closed until treated.

Recent History Similar ideas postulated for language (sensory pathways fixed after the critical period). - feral children?

New Evidence Suggests all areas of the brain are plastic, even into adulthood.

Neuroplasticity and Cortical Maps A. Sensory cortical map 1. an area deprived of input will become active later in response to inputs from adjacent cortical areas 2. the re-organization is not from cortical emergence - is from every level of the cortical hierarchy

Neuroplasticity and Cortical Maps B. Merzenich and Blake (2002) cortical implant studies 1. Plasticity is influenced by both sensory input and behavior. 2. When a stimulus is cognitively associated with reinforcement, its cortical representation is strengthened and enlarged. - can increase 2-3 fold in as little as one day

Neuroplasticity and Cortical Maps C. Doidge 1. separates plasticity into different categories based on behavioral consequences 2. positive plasticity - remodeling after a stroke 3. negative plasticity - excessive neuronal growth leading to spasticity or excessive neurotransmitter release

How Rapid is Neuroplasticity? Medical students' brains were imaged during the period when they were studying for their exams. In a matter of months, the students' gray matter increased significantly in the posterior and lateral parietal cortex.

Repair in the PNS A. Dependent on Schwann cells 1. Wallerian degeneration - axon downstream of injury - both neuronal tissue and myelin 2. endoneurial tubes remain behind - columns of Schwann cells (Bands of Bungner) - surrounding basal lamina (endoneurium)

Repair in the PNS A. Dependent on Schwann cells 3. Schwann cell basal lamina contains axon growth promoters - laminin - fibronectin - that is, at least, in vitro

Repair in the PNS A. Dependent on Schwann cells 4. Schwann cells produce neurotrophic factors a. nerve growth factor (NGF) - NGF mRNA  5-7 fold within 2 weeks - from Schwann cells and nerve fibroblasts

Repair in the PNS A. Dependent on Schwann cells 4. Schwann cells produce neurotrophic factors b. brain-derived neurotrophic factor c. glial cell-line derived neurotrophic factor d. leukemia inhibitory factor e. insulin-like growth factor f. fibroblast growth factor

Repair in the PNS B. Invading macrophages - stimulate Schwann cells and fibroblasts to produce NGF via macrophage-derived interleukin-1

Retinoic Acid Macrophages express retinoic acid receptors (RARs) and generate inflammatory cytokines, the production of which is inhibited by retinoic acid (RA). Schwann cells express RARs and sonic hedgehog (SHH). Maden, Malcolm. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nature Reviews Neuroscience 8, (October 2007)

Retinoic Acid Neurotrophins, for example, nerve growth factor (NGF), are induced after PND, and can act in both a paracrine fashion on the neuron and an autocrine fashion on the Schwann cell itself.

Retinoic Acid Damaged neurons are stimulated (possibly by neurotrophins from the Schwann cells) to produce RA from retinaldehyde dehydrogenase 2 (RALDH2), and also to produce SHH, which acts to supplement the beneficial effects of RA on axonal regeneration.

Repair in the PNS C. Occasionally inaccurate 1. cranial nerve III (oculomotor) - innervates several muscles that move the eye - also innervates levator palpebrae superioris 2. aberrant regeneration can cause eyelid to be raised when looking down

Repair in the PNS D. Loss of cell body leads to loss of axon 1. if motor - poliomyelitis - motor neuron disease (MND) 2. if sensory (dorsal root ganglia) - paraneoplastic syndromes antibodies to CNS parts triggered by a tumor leads to cell death