Neuromodulators

These are chemicals that basically have global effects on the entire brain, with neuron-type-specific effects on activity and plasticity. These global effects include some that can be best characterised as affective states or, dare I say, emotions.

• Dopamine
  • Positive valence, high arousal.
  • In early bilaterians: local search/exploitation (rewards are probably nearby).
  • Role in vertebrates: reward prediction error encoding for reinforcement learning. Earlier wrong hypotheses - reward signals, surprise signals.
  • Not a signal for pleasure itself, but for anticipation of pleasure. Elevated dopamine levels cause compulsive eating/exploiting behaviours without actual additional pleasure indicators or actual rewards.
  • Change from early bilaterians to vertebrates: fuzzy average of recent reward to precise probabilistically-calibrated reward expectations.
• Serotonin
  • Positive valence, low arousal.
  • In early bilaterians: rest-and-digest (satiation, rewards have already been found).
  • Elevated serotonin reduces responses to valence because it's a signal for already satiated.
• Norepinephrine, octopamine, epinephrine (adrenaline)
  • Negative valence, high arousal.
  • Signals acute stress. Triggers for escape behavior and fight-or-flight responses.
  • Energetically expensive. Bouts of adrenaline are usually followed by opioid responses that lead to recovery and pleasure.
• Opioids
  • Rest-and-recover after bouts of acute stress.
  • Work by enhancing serotonin and dopamine, and inhibiting negative-valence neurons.
  • Triggers prolonged feeding, inhibited pain responses, and inhibited reproductive behaviour.
  • Substantially increase liking-reactions, increasing pleasure and inhibiting pain, why they make for potent but addictive painkillers.
• Acetylcholine
• Noradrenaline

Chronic stress

Prolonged stress leads to a qualitative change in a process that is complex and not fully understood. It starts activating serotonin, turning down valence response and lowering arousal - numbness or anhedonia. Animals no longer respond much to stimuli, good or bad.

Combinatorial neuromodulation

Nikolas Karalis at the FMI, now in Paris, makes a good case for the fact that these need to be studied in terms of their joint action, what he calls the combinatorial neuromodulations.

• Has good data on simultaneous recordings of all neuromodulator concentrations and electrophysiological recordings from the amygdala.