Critical periods A time period when environmental factors have especially strong influence in a particular behavior. –Language fluency –Birds- Are you my mother? –eye-specific layers in lgn and visual cortex

There is a Critical Period for Learning Language

Manual "Babbling" in Deaf Infants With Deaf, Signing Parents Compared to Manual "Babble" in Hearing Infants PN24010.JPG

Konrad Lorenz and his geese (Photo by Tom McAvoy; courtesy of LIFE Magazine, ©1955, Time, Inc.)

Birdsong

Development as an active process Frog brainFrog

Development as an active process Optic tectum Eye

Development as an active process ? Optic tectum Eye

Development as an active process

Critical periods in visual development Visual system is a model system to study mechanisms of plasticity. Retina to LGN to visual cortex. LGN and layer 4 of cortex have monocular inputs. Cells in other layers of cortex can get inputs from both eyes.

Columnar Organization of Ocular Dominance (review)

PN24040.JPG Effect of Early Closure of One Eye on Distribution of Cortical Neurons Driven By Stimulation of Both Eyes

Consequences of brief Monocular Deprivation at the Critical Learning Period in the Cat

Ocular Dominance: Single-cell Recordings in Normal and Strabismic Cats

Cat cortex, mask-raised. Each row is a different cell.

Other experiments Closing both eyes > relatively normal distribution of inputs. Implies that it is not atrophy of unused circuits that causes the deprived eye to lose out, but competition that allows one eye to win.

Other experiments Closing both eyes > relatively normal distribution of inputs. Implies that it is not atrophy of unused circuits that causes the deprived eye to lose out, but competition that allows one eye to win. Tracing of single neurons in LGN shows that visual activity influences arborization of axons, lack of activity leads to less branching.

Terminal Arborizations of LGN Axons Can Change Rapidly in Monocular Deprivation reduced number of branches in deprived eye

Transneuronal Labeling With Radioactive Amino Acids

Ocular Dominance Columns in Layer IV of the Primary Visual Cortex of an Adult Macaque Monkey

How do neurons know that they are around others of the same eye? Hebb’s postulate When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.

How do neurons know that they are around others of the same eye? Hebb’s postulate When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased. Correlated activity between presynaptic and postsynaptic cells strengthens synaptic connections between them. Cells that fire together, wire together. Also used in learning and memory, called long term potentiation (LTP).

Hebb's Postulate During Visual System Development

Long Term Potentiation [LTP] Brief high frequency train of inputs leads to a long-lasting increase in EPSP amplitude. LTP does not occur at all synapses, only those that are stimulated. > Learning and memory. Would not want to strengthen synapses that didn’t correlate with a stimulus. Time scale: days, weeks ????

What does Calcium do? Ca stimulates multiple Ca++ dependent protein kinases Mice mutant in these kinases have defects in LTP, learning, and memory. –Kinases Get more AMPA receptors into the spine. More receptors = more depolarization in response to glutamate. Grow more spines = increases number of synapses with a give neuron

Long-term depression ( LTD) is the opposite of long-term potentiation (LTP). Cells become less sensitive to input. Occurs when communication across the synapse is silenced or weakened. (stimulation at a low rate over long period) LTD is important in the cerebellum, in procedural memory, where the neurons involved in erroneous movements are inhibited by the silencing of their synaptic connections. LTD allows us to correct our motor procedures when learning how to perform a task. (e.g. – forgetting the way that was a mistake so you don’t keep doing it) Like LTP – can occur in several brain regions – especially hippocampus and cerebellum Long-Term Depression

LTD in cerebellum: Depolarization of post-synaptic cell Glutamate activates both AMPA and Mglu Indirectly triggers clatharin- dependent internalization of AMPA receptors This weakens the synapse In hippocampus – similar mechanism.

Long-term depression Weakens inputs (forgetting?). Low frequency tetanus leads to long-term depression of synapses. Has all the same properties as LTP. Requires NMDA receptors, Ca. Small rises in Ca++ lead to depression whereas large increases in Ca++ trigger potentiation. Cam Kinase required for LTP, Ca++ dependent phosphatase required for LTD.

Conclusions Experience can change behavior. Experience can change patterns of synaptic connections. Neural activity is required to make these changes. Changes are easier early in development, during critical periods.