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Neurotransmitters and
Behavioral Development
Byron C. Jones
The Pennsylvania State University
Outline of Presentation
• Behavioral development has multiple
potential trajectories
• An epigenetic view of behavioral
development
• The role of neurotransmitters in
behavioral development and vice versa
The Pluripotency of Behavior
• In vertebrates, behavioral systems are generally not
“hard wired”, although many show some sort of
preparedness based on biological constraints
• Most behavioral systems demonstrate wide individual
differences in expression, magnitude, topography,
etc.
• Most behavioral systems are subject to “critical
periods” – or sensitive periods during development –
these are intervals during which the individual is
maximally sensitive to environmental events that
influence the behavior
Behavioral Development: An
Epigenetic View
• Epigenesis was coined by Wadsworth in
the 1930s as a template to describe and
define embryological development
• Accordingly, epigenesis is defined as
the interplay between genes and the
environment that “canalize” the course
of development
Environment
Gene
Protein
Hormones, Behavior
NTs
Affective
Consummatory
Cognitive
Pharmacology
Motor
Add the dimension of time and this is how we can view the
contribution of genes and the environment to behavioral
development
What IS the Environment?
• External
– Nutrients, toxins, ambient conditions,
perturbations
• Internal
– Hormones, neurotransmitters, proteins
(that affect gene expression), electrolytes,
metabolites, etc.
External Environmental
Influences on Neurotransmitters
• The pioneering work at UC Berkeley on
early environmental enrichment and ACh
systems
– Increased cortical thickness
– Increased AChE
– Increased exploration, etc.
• The pioneering work by Levine at
Stanford on early stress and HPA
activity and related behavior
Some Experimental Evidence
• Gariepy, Rodriguiz and Jones, 2002
– Study of experimentally administered
different environments during development
in lines of mice selected for high and low
aggression.
– Handling vs undisturbed
– Group vs Isolate housing
Spontaneous Activity
• Open field ambulation
• Unsupported rearings
Corticosterone Response to Testing
• Serum collected 20 min after
introduction into the open field
• Corticosterone measured by RIA
• Baseline corticosterone values obtained
in separate animals, nonhandled, not
isolated.
Dopamine D1 receptor densities
• After open-field testing animals were
killed by halothane overdose, and the
brains removed with caudate-putamen
and nucleus accumbens dissected.
• Maximum binding for 3H-SCH 23390 in
membrane fragments
• No effects of handling or isolation in
the caudate-putamen
• Nucleus accumbens….
Isolate Housed
Group Housed
Aggressive/Fear-like Behaviors
•
•
•
•
Latency to attack an intruder..
Latency to freeze..
Attacks
Freezing episodes
Conclusions
• HPA system seems to be the target of
GXE sensitivity
• Aggression also seems to be sensitive
• Dopamine system seems to be
refractory
• Moral of the story – not all systems in
an organism are equally susceptible
The Internal Environment
• There are large inter-individual
differences in neurotransmitter
systems
• Most of these systems are analyzed in
adult animals – so there are
developmental questions to be asked
Dopamine and Ethanol
Consumption
• Genetic-based differences in dopamine
D1 receptor in caudate-putamen
• Ethanol acceptance
• Problem here is we don’t know the
developmental trajectory
Effects of Neurotransmitters on
Development
• 5HT as a neurotrophic factor
– Probably operates through 5HT1a receptors
to affect synthesis of BDNF
– Influences arborization in granule cells in
hippocampus
• What does this mean?
– Importance of 5HT in depression –
constituitively low tone as a risk factor?
– Antidepressants and hippocampal cell repair
What’s the Take-Home Message?
• There is a wide range of inter-individual
differences in neurotransmitter biology
• These differences come from genetic
makeup, the environment and GXE
interaction
• While the environment can influence
neurotransmitter function, constitutive
differences in NT can influence other
neurobiological and behavioral systems