The Nature part of nature/nurture for learning

✿ A gene is a part of a chromosome. Genes are in pairs

✿ Genes affect our learning ability

✿ A chromosome consists of a double-stranded chemical = DNA

z Each pair (23 in humans) splits apart taking its genes with it

z Sometimes can get the genes from the other chromosome by a process called `crossing over’

z Natural selection is not good or bad. z It just happens. z Most of the mutations that occur are

deleterious.

Darwin exploring

Evolution of traits

Natural selection (Natura)

There was probably one ancestor from one place- Africa.

z All modern people can trace their heritage to Africa. y DNA samples of 12,127 men from 163 Asian

and Oceanic populations. y Every one of the subjects carried a mutation at

one of 3 genetic markers on the Y Chromosome.

x Those three sites can be traced back to a single African population some 35,000 to 89,000 years ago.

z Although there was probably one population, several species of early man may have appeared and died out.

z Somewhere between 200,000-500,000 years ago some migrated out of Africa (Lemonick, 1994; Harris and Hey, 1999).

All children from the same mother have identical mitochrondrial DNA

z Africa has been shown to be the actual birthplace of Eve at 200,000 years ago on the basis of mtDNA (Cann, Stoneking, and Wilson)

z mtDNA change only by mutation (1-2% every 100,000 years).

z Each chance mutation is preserved in the next generation

50 genes =cognitive differences between man and ape.

z Just 50 out of 140,000 genes that humans and chimps are thought to possess (0.3%) may account for all of the cognitive differences between man and ape. y Chimps and gorilla are more closely

related to humans than they are to orangutans (Jean-Jacques Hublin)

Humans = a third race of chimpanzees.

z From our DNA, humans appear from a genetic perspective as a third race of chimpanzees.

z Although chimps took a different evolutionary path from humans about 8 (9?)? million years ago, they share 98.4 percent of our DNA.

z In comparison, on the average humans share 99.8 percent of the same genetic material (Lewontin, 1972).

There are Learning and memory genes

z during learning (STM) and memory (LTM) new genes are expressed that are required to establish long-term memories.

z There are specific genes devoted to memory storage.y most identified as affecting memory

are involved in signal-transduction pathways for purposes unrelated to memory

Evolution of Gene Related to Brain's Growth

z Genes affect the evolution of the cortex.

z A gene (ASPM) helps determine the size of the human brain.y ASPM has been under

intense Darwinian pressure in the last few million years,

y changed its structure 15 times since humans and chimps separated from their common ancestor.

Formation of memories

z If neuron fires often and strongly it is declaring that this is an event that should be recorded and the relevant genes turn on.

z The synapses holding STM are made by proteins and become tatooed into LTM.

LTM (long-term memory)

z Long-term strengthening of synaptic connections involvesy the induction of new

genes in the neuron

y an increase in the number of functional synapses

Genes know when to strengthen a synapse.

Genes manufacture synapse-strengthening proteins.

The cell’s nucleus “listens” to the cell’s action potential to determine when to strengthen a synapse and make a memory last.

CREB is turned on by genes and vice versa

z CREB= a molecular switch for the formation of LTM.

z CREB is required for the stability of initial and reactivated memories.

Gene zif268 is associated with learning and memory.

z It is turned on by hippocampal neuron firing.

z When the membrane depolarizes the machinery in the nucleus listens to the output of the neuron to decide whether to synthesize memory-fixing proteins.

Turn on active Genes genes

knockout-mouse or fly (Drosphilia)

z tells us what genes are necessary to develop a normal learning and memory phenotype in the adult.

z These knockout lines do not give us access to all the molecules in the adult brain that participate in memory encoding.

z Knockout fly used in experiment in next movie clip.

Master genes rule cascade of genes genes1

Learning genes in Drosphilia

z 4 mutants obtained from behavioral screens: dunce, rutabaga, amnesiac and linotte.

y (3 of the 4 mutants affect molecules that are involved in learning).

z the mutant dunce seemed to affect learning the most

Environmental modification of heritable behaviors (nature + nurture)

z Nature: Different Genetic strains of mice

bred to be smart. in an elevated maze. swimming (Japan conf).

z Nature + Nurture: Phenylketonuria (PKU)- genetic inability to metabolize amino acid phenylalanine. y Can lead to retardation. y Can control by diet.

Nurture: environmental enrichment

z improved performance of rats in a water maze

z tended to increase activity of CREB in the hippocampus.

Nurture Deficient folate = cognitive impairment.

z children born to severely folate-deficient mothers often have abnormal or delayed intellectual development.

z taking adequate folate during pregnancy has been proven to cut nervous system birth defects by 50%.

z low folate - associated with depression + dementia in the elderly.

Neuron on right from animal in stimulating environment=more branches

AT BIRTH 3 MONTHS 2 YEARS

Can either enhance or retard the normal development of the brain by the type of environment

Thymidine study

The development of the brain as shown by splitting and migration

of DNA

My research using the DNA in our genes to look at how our brain develops.

z Pick a more primitive species.

z Look at parts of the new brain= the thalamus and neocortex.

z Those are what is important for higher processes such as learning.

monodelphis opossum= short tailed gray opossum= Brazilian opossum

z Use of a marsupial, the monodelphis opossum.

z This allows us to insert Thymidine in the embryo.

Development of the thalamus in gray short-tailed opposum (J. of Mammalogy).

z Advantage of development in a marsupial= the embryos can received direct injections.

Thymidine

z Thymidine is taken up in the DNA `mother cells’.

z They split into `daughter cells’ (with half as much DNA) etc.

z The daughter cells and granddaughter cells migrate to their final place of work.

Tritiated Thymidine

z The Thymidine is radioactive and so can be detected by its reactivity on an emulsion coat put over the brain tissue (which is mounted on a slide).

Tritiated thymidine was injected into the monodelphis domestica at embryonic ages -3 through day +16.

Plotting for documentation of location

z My job is to document the location within the brain of the mother cells, daughter cells etc.

z I focused on the thalamus which is the central place for all of the information either going to the cortex or descending from the cortex= It is critical for all cortical activity.

Purpose of the study

z From this work we learn about how the brain develops.

z There are critical periods where the brain is more susceptible to damage. These would be more prevalent in the period before the neurons have migrated to their final position.

results

The thalamus Develops at theSame time asThe cortex. CortexSame as the brainstemIn that way. Easier to Repair?

Stem cell research

z This work can help with stem cell research studies.

z Tissue that is not yet fully differentiated is more likely to be able to become another part of brain tissue.

z Someday brain repair or partial brain transplants may be a possibility for humans.

Stem cells (1)

z See you next time