Baldassarre, Gianluca

Cabib, Simona

Fiore, Vincenzo G.

Mannella, Francesco

Mirolli, Marco

Puglisi-Allegra, Stefano

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A Computational Model of Stress Coping in 
Rats
Vincenzo Fiore1*, Francesco Mannella1, Marco Mirolli1, Simona Cabib2, Stefano Puglisi-Allegra2 and 
Gianluca Baldassarre1 
• 1 Consiglio Nazionale delle Ricerche (LOCEN-ISTC-CNR), Laboratory of Computational 
Embodied Neuroscience, Istituto di Scienze e Tecnologie della Cognizione, Italy 
• 2 Universita degli studi di Roma La Sapienza, Department of Psychology, Italy 
This work presents a computational neural-network model explaining the brain processes underlying 
stress coping in rats exposed to long lasting inescapable stress conditions, focussing on the three 
neuromodulators dopamine (DA), noradrenaline (NE) and serotonin (5-HT). The importance of the 
model relies on the fact that stress coping experiments are considered a good animal model of the 
mechanisms underlying human depression. Pascucci et al. (2007) used microdialysis to investigate the 
correlation existing between the presence of NE and DA in medial prefrontal cortex (mPFC) and the 
quantity of mesoaccumbens DA during a restraint test lasting 240 min. The comparison of the 
microdialysis results related to sham rats and rats with either NE or DA depletion in mPFC showed the 
role played by such neuromodulators on DA release in nucleus accumbens (NAcc) and the 
active/passive modality of stress coping.
In the model, the stressing stimulus initially activates a first group of neural systems devoted to active 
stress-coping and learning. The amygdala (Amg) activates the subsystems NAcc-shell/infralimbic-
cortex (NAccS-IL) and NAcc-core/prelimibic-cortex (NAccC-PL). The latter subsystem is responsible 
for triggering actions that may terminate the stressing stimulus, whereas the former is responsible for 
(learning) the selected inhibition of those 'neural channels' of actions which are executed but fail to stop 
the stressing stimulus. 
The ability of actively coping with stress (lasting about 120 min in experiments) and learning which 
actions have to be avoided as ineffective is modulated (either depressed or enhanced) by the presence 
of the three neuromodulators targeting the Amg-NAcc-mPFC systems. Amg activates the locus 
coeruleus (LC) which in turn produces NE, enhancing the activity of Amg, NAccS and mPFC. The 
activity in mPFC activates the mesoaccumbens module of the VTA which releases DA, enhancing the 
activity of NAcc. Passive stress coping, which follows active coping, is caused by both the release of 5-
HT in the Amg-NAcc-mPFC systems and the VTA release of DA in mPFC. The cause of the shift from 
active to passive coping is assumed to be in the PL and its inhibitory control of the activity of the dorsal 
raphe (DR): when this inhibition terminates due to the IL inhibition of PL, the DR starts releasing 5-HT 
(Maier and Watckins, 2005), activating at the same time the mesocortical VTA via glutamatergic 
synapses. 
The model has an architecture wholly constrained by the known brain anatomy and it reproduces rather 
in detail the micro-dialysis recordings of the slow dynamics (tonic) of DA and NE in mPFC and NAcc 
(e.g. see charts comparing microdialyses and simulations). On this basis, the model offers for the first 
time a coherent and detailed computational account of brain processes during stress coping. 
References
1. Maier F.S., Watkins R.L. (2005). Stressor controllability and learned helplessness: The roles of the 
dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neuroscience and Biobehavioral 
Reviews, 29, 829-841.
2. Pascucci T., Ventura R., Latagliata E.C., Cabib S., Puglisi-Allegra S. (2007). The medial prefrontal 
cortex determines the accumbens dopamine response to stress through the opposing influences of 
norepinephrine and dopamine. Cerebral Cortex, 17, 2796-804.
Conference: Bernstein Conference on Computational Neuroscience, Frankfurt am Main, Germany, 30 
Sep - 2 Oct, 2009. 
Presentation Type: Poster Presentation
Topic: Dynamical systems and recurrent networks 
Citation: Fiore V, Mannella F, Mirolli M, Cabib S, Puglisi-Allegra S and Baldassarre G (2009). A 
Computational Model of Stress Coping in Rats. Front. Comput. Neurosci. Conference Abstract:  
Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.neuro.10.2009.14.050
Received: 26 Aug 2009; Published Online: 26 Aug 2009. 
* Correspondence: Vincenzo Fiore, Consiglio Nazionale delle Ricerche (LOCEN-ISTC-CNR), 
Laboratory of Computational Embodied Neuroscience, Istituto di Scienze e Tecnologie della 
Cognizione, Rome, Italy, vincenzo.g.fiore@gmail.com


A computational model of stress coping in rats

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A computational model of stress coping in rats

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