Notes

Some Major Circuits in Aversion Processing: Focus on Habenula and Tegmentum In order to understand more of the behavioral responses, we have to go in the Periaqueductal Gray (PAG) or the Rostromedial Tegmental Nucleus (RMTg). There is a projection from the central amygdala to the PAG, so the GABAergic neurons are sending long-range projections.

Some Major Circuits in Aversion Processing: Focus on PAG, LHb, RMTg The Periaqueductal Gray contains GABAergic neurons targeted by GABA neurons from the central amygdala which are projecting to glutamate neurons in the PAG. When the neurons in central amygdala fires (i.e., when the lateral amygdala detects a CS or US) then they will inhibit GABA neurons in PAG, which will disinhibit Glutamate neurons in the PAG, these neurons project then to the Lateral Habenula (LHb) which excites VTA GABA interneurons and Rostromedial Tegmental Nucleus (RMTg) , which is in turn capable of inhibiting the dopamine neurons in the Ventral Tegmental Area (VTA). Hence, one of the key features of aversive stimuli processing is the inhibition of dopamine release, which is one of the main neurotransmitters underlying reward behavior.

Neural Circuitry of Pavlovian Aversion Behaviour Unconditioned response is Flight, Conditioned response is Freezing. If the neural circuitry underlying conditioned and unconditioned stimuli is the same, how is it possible that the reaction elicited is different?

Amygdala to PAG Pathway In Mouse, optogenetic excitation (ChR2) of dorsal Periaqueductal gray (dPAG) glutamate neurons causes: (1) Increased Running/Flight during dPAG neuronal firing. (2) Increased Freezing after dPAG neuronal firing.

It suggests 2 separate populations of neurons in dPAG: (1) Neurons for UR = Flight. (2) Neurons for CR = Freeze.

Importance of LHb/RMTg to Dopamine-Neuron Circuit to Aversion Processing Experiment in Macaques: a point is showed on a computer screen. If the point moves in a direction, then it is predictive of a tone and a reward. If the point moves in the other direction, then there is a different tone and no reward coming. Here the absence of reward is the aversive stimulus. What was seen is that:

• No-Reward CS results in phasic excitation of LHb neurons and phasic inhibition of VTA DA neurons.
• Reward CS results in phasic inhibition of LHb neurons and phasic excitation of VTA DA neurons. In the case of rats:
• Aversive CS or US results in phasic excitation of RMTg GABA neurons.
• Reward CS or US results in phasic inhibition of RMTg GABA neurons.

Some Major Circuits in Aversion Processing: Focus on Prefrontal Cortex Medial Prefrontal Cortex has long-range Glutamate connections to the Amygdala Basolateral complex (BLA) and the Nucleus Accumbens. It also receives dopaminergic neurons from VTA. PFC is fundamental in goal-directed behaviour.

Aversion Learning: Importance of Prefrontal Cortex to Amygdala Circuit In Mouse, Optogenetic excitation of infralimbic Prefrontal Cortex (vmPFC) glutamate neurons projecting to Basomedial amygdala (BMA) decreases freezing behaviour related to Pavlovian (CS-US) aversion learning - increased extinction learning (gradual decrease in response to a conditioned stimulus that occurs when the stimulus is presented without reinforcement) (Similar behavioural effect is observed with optogenetic excitation of BMA Glutamate neurons directly).

Overview of a Major Neurocircuit in Aversion Processing and Subsequent Behaviour