Abstract
Background
Learned associations between environmental stimuli and rewards play a critical role
in addiction. Associative learning requires alterations in sparsely distributed populations
of strongly activated neurons, or neuronal ensembles. Until recently, assessment of
functional alterations underlying learned behavior was restricted to global neuroadaptations
in a particular brain area or cell type, rendering it impossible to identify neuronal
ensembles critically involved in learned behavior.
Methods
We used Fos-GFP transgenic mice that contained a transgene with a Fos promoter driving
expression of green fluorescent protein (GFP) to detect neurons that were strongly
activated during associative learning, in this case, context-independent and context-specific
cocaine-induced locomotor sensitization. Whole-cell electrophysiological recordings
were used to assess synaptic alterations in specifically activated GFP-positive (GFP+)
neurons compared with surrounding nonactivated GFP-negative (GFP−) neurons 90 min
after the sensitized locomotor response.
Results
After context-independent cocaine sensitization, cocaine-induced locomotion was equally
sensitized by repeated cocaine injections in two different sensitization contexts.
Correspondingly, silent synapses in these mice were induced in GFP+ neurons, but not
GFP− neurons, after sensitization in both of these contexts. After context-specific
cocaine sensitization, cocaine-induced locomotion was sensitized exclusively in mice
trained and tested in the same context (paired group), but not in mice that were trained
in one context and then tested in a different context (unpaired group). Silent synapses
increased in GFP+ neurons, but not in GFP− neurons from mice in the paired group,
but not from mice in the unpaired group.
Conclusions
Our results indicate that silent synapses are formed only in neuronal ensembles of
the nucleus accumbens shell that are related to associative learning.
Keywords
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Article info
Publication history
Published online: August 14, 2015
Accepted:
August 6,
2015
Received in revised form:
August 5,
2015
Received:
June 18,
2015
Identification
Copyright
© Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry
