Neurogenetics

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Neurogenetics

• Chapter 7

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Neurogenetics

• Functional genomics How genes interact to
  produce behaviour
• Neurogenetics Genetic analysis of brain
  structure and function as it relates to behaviour
• Methods
• Induced mutations
• Targeted mutations
• Naturally occurring genetic variation
• Chips for DNA expression
• Antisense DNA

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Induced mutations Circadian rhythms

• Drosophila timeless and period
• Negative feedback for transcription inside the
  nucleus.
• Period 24 hrs cycle, timeless is light dependent
• Found in other species silkworms, cockroaches,
  bees, humans evolutionary function
• Affects other behaviours when transferred between
  species.

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Induced mutations Circadian rhythms

• Clock gene in mice
• Mutations to the gene cause one hour delay in
  heterozygous and four in homozygous
• Could be rescued when wild genes are inserted
  in mutants
• Concept of pacemaker
• SCN is pacemaker in hypothalamus
• Sensitive to light and other brain influences
• Has effects upon other functions (endocrine,
  metabolic, memory)

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Induced mutationsLearning and memory

• Numerous genes involved as per mutation analysis
• Five genetically distinct temporal phases
• Acquisition
• Short term (STM)
• Middle term (MTM)
• Anesthesia resistant (ARM)
• Long term (LTM)

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Induced mutationsLearning and memory

• cAMP as a mediator of memory
• cAMP responsive element (CRE) activated by
  protein kinases
• Stabilizes memory by changing expression of genes
  and making synapses stronger
• Pairing stimuli effective in establishing memories

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Targeted mutationsLearning and memory

• Focus on hippocampus
• a- Ca2-calmodulin kinase II
• Expressed after birth
• Mutants did not learn as well as wild mice did
• Hebbian concept of storage in neural circuits

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Targeted mutationsLearning and memory

• Long term potentiation
• a-CAMKII gene activates expression of CRE binding
  protein (CREB)
• If CREB is reduced LTP is not produced
• Conditional knock out in Drosophila dependent on
  temperature
• NMDA receptor switch for coincident firing of
  neurons by acting on cAMP
• NMDA decreases with age
• Conditional knock out increased life span of NMDA
  and enhanced learning

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Learning and memory

• Gene actions not specific to a particular
  function
• Other methods are functional and metabolic (PET
  scans and fMRI)
• Pharmacogenetics and memory studies
• Problems with KO compensation, lack of control,
  cost, rate of success, etc.

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Antisense DNA

• DNA sequence complementary to a mRNA (18-25 bp)
• Prevents translation
• High temporal and spatial resolution
• Used in preventing synthesis of receptors for
  drugs

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Chips

• Coordinated expression of thousands of genes
• Oligonucleotides embedded in a matrix
• Washed with sample
• Expressed genes stick to oligoucleotides
• Later detected

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Naturally occurring mutations

• Remember mutations may express themselves
  differently in different strands
• A gene has many different functions
• A gene does NOT have a well defined behavioural
  function

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Functional genomics

• Move to find genes to find pathways from genes to
  behaviour
• Synaptic plasticity
• Behavioural genomics may be more useful in
  prediction diagnosis, intervention and prevention
  of behavioural disorders