Eric Kandel formulated a sketchy theory of motivation as based on serotonergic co-activation of glutamatergic synapses. When a stimulus is emotionally strong, there is a release of serotonin in addition to the release of the glutamate that carries the sensory message. The co-activation of the post-synaptic neuron reinforces the learning of the stimulus and the formation of long-term memory by means of the activation of a signal-transduction pathway from the membrane receptors to transcriptional factors, leading to the production of more of the same membrane receptors and growth factors. The memory of the pattern of the stimulus becomes embodied in the new formed connections . Without the serotonergic reinforcement, these connections would not be formed.

Other approaches to monoaminergic reinforcement of glutamatergic synapses have focused on dopamine. A common target for glutamate and dopamine was found, the protein DARPP-32 (see link). Together with the kinases activated by calcium ion entry through NMDA channels, that protein could help to understand the mechanism of differential learning (learning with motivation) in single cells.

However, a mechanism of inter-cellular differential learning was missing. How is a large cell assembly coordinated (by motivational factors) to learn a pattern and to retrieve it consciously later? Inspired by a cognitive experiment made in the classroom with my students, showing that interesting information presented just one time (for two seconds) could be more remembered than uninteresting information presented two or three times (for two seconds each time), I proposed that the astroglial inter-cellular calcium wave could be such a mechanism (se link 2).

More recently, the hypothesis of astroglial involvement in motivation received an indirect confirmation from a series of experiments made by Maiken Needergard with her post-docs (having Ding and O'Donnell as first author; see link 3). They showed that norephinephrine/noradrenaline is a major inductor of large calcium waves in vivo.

These results point to an integrative view of four main modulators of emotional feelings, as reviewed in Wang and Pereira Jr. (2016; see link 4).

https://www.ncbi.nlm.nih.gov/pubmed/14744247

https://www.ncbi.nlm.nih.gov/pubmed/?term=calcium+wave+model+pereira+barros

https://www.ncbi.nlm.nih.gov/pubmed/24138901

Article Neuromodulation, Emotional Feelings and Affective Disorders

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