Varieties of behavioral natural variation

by Patrick T. McGrath

Current Opinion in Neurobiology 2012, 23: 1-5

- Behavioral variation in different time scales: 

1) learning or experience driven changes

2) evolutionary change

- The genetic basis of heritable behavioral differences is complex with multiple genetic variants of small effects.

- How genetic differences between individuals cause behavioral difference?

- Many trait differences are caused by a complex combination of genetic changes distributed throughout the genome.

- Coding changes, duplications, small noncoding RNA changes, cis -regulatory changes, neural specific alternative splicing changes

- How do the underlying genetic networks impact the types of genetic variants?

Comparison and contrast between evolution of behavior and development

- Development of body - largely controlled by gene

- Development of Behavior - genetic, acquired information, environment, internal state

Evolution of sensory systems

Three drivers for sensory evolution

1) Change of environment - heterogenetic, changing both spatially and temporally

2) Animals only sense a subset of their environment or stimuli that are also changing 

3) Animals obtain information through proxies that can be sensed

1) Evolution of sensory genes reproducible upon an environmental shift

- Strains of C. elegans grown at high density for long periods of time have become resistant to dauer-inducing pheromones

- This is caused by deletions of pheromon receptor genes

2) Evolution of a metabotropic bioamine receptor 

- Changes in connection between behavior state and sensory systems

- Changes nearby tyra-3 gene (G-protein-coupled receptor for norephinephrine) 

- Increased expression of tyra-3 in a pair of sensory neurons correlated with and sufficient to cause a decreased frequency of leaving a depleting food source.

- The genetic change seems to modify how an internal state of the animal affects behavior. 

- Changes are not only in genes themselves but changes in regulation of these genes at cis-regulatory regions.

Neuromodulator-evoked synaptic metaplasticity in a CPG

Mark D. Kvarta, Ronald M. Harris-Warrick and Bruce R. Johnson

Metaplasticity (Philpot et al. 1999): Characteristics of activity-dependent changes in synaptic strength altered by neuromodulation (Fischer et al. 1997; Kreitzer and Regehr 2000; Parker 2001; Parker and Grillner 1999; Qian and Delaney 1997).

In this study, the authors showed amines (5-HT, DA, and OA) change the properties of homosynaptic plasticity of a specific graded synapse in STG. The synapse used in this study was PD-to-LP synapse. This is apparently due to modification of vesicle traffic dynamics but the authors did not further dig experimentally into the vesicle release dynamics referring to the readily releasable pool sizes and replenishment rates. Recovery rate of homosynaptic depression was also dependent on the presynaptic activity. The authors discussed that maintained presynaptic depolarization would cause more calcium influx, which consequently increases mobilization of the recovery process.

Dopamine had reliable, significant and independent effects to accelerate the time course of synaptic depression onset and recovery from synaptic depression. It consistently accelerated both the onset of, and the recovery from, synaptic depression. This acceleration of onset and recovery from depression did not depend on the sign of the rather variable DA effect on gIPSP amplitudes described above.

DA had weak and highly variable effects on the LP gIPSPs in different preparations. It increased the rate of synaptic depression and of recovery from it. The variability to DA responses cane be caused by the known opposing effects of DA to decrease pre-synaptic PD transmitter release and increase post-synaptic LP input resistance (Harris-Warrick and Johnson 2010), but to differing amounts in different preparations.

DA may be acting postsynaptically to accelerate the kinetics of transmitter receptor desensitization and recovery from desensitization (Papke et al. 2011).

Octopamine - Increased both initial and steady amplitude, slowed the onset of synaptic depression, while speeding up the recovery rate from depression.

- What about contribution of post-synaptic receptors?

Serotonin - Serotonin depresses the synapse and accelerated the time course of synaptic depression measured with square pulse PD stimulation, but not reach statistical significance for oscillation.

The authors stated in the discussion that individual parameters of synaptic strength can be independently modulated by each amine. I disagree. The synaptic strengh should be determined by the fraction of readily releasable pool activated by depolarization, which must be under a strong influence of the vesicle replenishment rates. I don't think they are independent.