Model Systems
• Neuroscientists study a range of animals but much of the work is concentrated on groups which were economically
important → insects or had very accessible nervous systems and characteristic behaviours → molluscs
• Caenorhabditis elegans (1998) and Drasophila melanogaster (2000) first animals to have their genome sequenced →
allow evolutionary comparisons to be made
• C. elegans
o 1090 cells; 302 neurones; 5600 synapses; 2000 NMJs
o Simple methodology for producing gene knockout using double stranded RNA injected into egg region or fed
using vector strain E. coli
o Neural mutants of C. elegans
▪ Behavioural mutants → changes in chemotaxis; touch sensitivity; food processing; egg-laying
▪ NT mutants → cells lacking GABA phenotype ‘bag of worms’
▪ Cell death mutants → programmed cell death important in development → 131/1090 cells (105
neurones) programmed death. Mec4 controls degeneration of touch receptors
▪ Many loss or gain of function mutants produced by knockout genetics
• Drasophila melanogaster
o More complex nervous system and cell lineage
o Extensive chromosomal mapping, genetic and molecular tools available
o Economically relevant pest
o Established methods for transgenics
o Used as a tool for Neurobiology
▪ Behavioural mutants identified
▪ Memory mutants → Dunce and Rutabaga
▪ Photoperiod mutants
▪ Knockout and knock-in genetics used to study roles of many genes
▪ Identification of many of gene families involved in development
o Drasophila and memory
▪ Dunce mutant shows defective learning and memory – genes codes for cAMP phosphodiesterase.
cAMP levels up to 6x higher in Dunce. Seen as disruption of STM
▪ Rutabaga shows defect in cAMP forming enzyme adenylate cyclase → defective STM
▪ In flied engineered to express blocker of CREB function, LTM disrupted
• VGPCs
o Involved in repolarization of membrane during AP
o Attempts to purify and identify channel protein were unsuccessful for many years due to the lack of
molecular tools such as toxins which could bind to the channel with high affinity (compared with scorpion
toxin and sodium channels)
• Shaker Locus (encodes VGPCs)
o Using genetic maps, identified position of shaker to cloned segments of DNA – positional cloning
o ¼ size of VGS/CC – homology with each of the 4 domains of sodium or calcium channels
o Highly variable die to alternative splicing of exons producing channels with different properties
• Neuroscientists study a range of animals but much of the work is concentrated on groups which were economically
important → insects or had very accessible nervous systems and characteristic behaviours → molluscs
• Caenorhabditis elegans (1998) and Drasophila melanogaster (2000) first animals to have their genome sequenced →
allow evolutionary comparisons to be made
• C. elegans
o 1090 cells; 302 neurones; 5600 synapses; 2000 NMJs
o Simple methodology for producing gene knockout using double stranded RNA injected into egg region or fed
using vector strain E. coli
o Neural mutants of C. elegans
▪ Behavioural mutants → changes in chemotaxis; touch sensitivity; food processing; egg-laying
▪ NT mutants → cells lacking GABA phenotype ‘bag of worms’
▪ Cell death mutants → programmed cell death important in development → 131/1090 cells (105
neurones) programmed death. Mec4 controls degeneration of touch receptors
▪ Many loss or gain of function mutants produced by knockout genetics
• Drasophila melanogaster
o More complex nervous system and cell lineage
o Extensive chromosomal mapping, genetic and molecular tools available
o Economically relevant pest
o Established methods for transgenics
o Used as a tool for Neurobiology
▪ Behavioural mutants identified
▪ Memory mutants → Dunce and Rutabaga
▪ Photoperiod mutants
▪ Knockout and knock-in genetics used to study roles of many genes
▪ Identification of many of gene families involved in development
o Drasophila and memory
▪ Dunce mutant shows defective learning and memory – genes codes for cAMP phosphodiesterase.
cAMP levels up to 6x higher in Dunce. Seen as disruption of STM
▪ Rutabaga shows defect in cAMP forming enzyme adenylate cyclase → defective STM
▪ In flied engineered to express blocker of CREB function, LTM disrupted
• VGPCs
o Involved in repolarization of membrane during AP
o Attempts to purify and identify channel protein were unsuccessful for many years due to the lack of
molecular tools such as toxins which could bind to the channel with high affinity (compared with scorpion
toxin and sodium channels)
• Shaker Locus (encodes VGPCs)
o Using genetic maps, identified position of shaker to cloned segments of DNA – positional cloning
o ¼ size of VGS/CC – homology with each of the 4 domains of sodium or calcium channels
o Highly variable die to alternative splicing of exons producing channels with different properties
