Unpredictable chronic mild stress (CMS) is among the most popular protocols used to induce depressive-like behaviors such as anhedonia in rats. Differences in CMS protocols often result in variable degree of vulnerability, and the mechanisms behind stress resilience are of great interest in neuroscience due to their involvement in the development of psychiatric disorders, including major depressive disorder. Expression of depressive-like behaviors is likely driven by long-term alterations in the corticolimbic system and by downregulation of dopamine (DA) signaling. Although we have a deep knowledge about the dynamics of tonic and phasic DA release in encoding incentive salience and in response to acute/chronic stress, its modulatory action on cortical synaptic plasticity and the following implications on animal behavior remain elusive. Here, we show that the expression of DA-dependent synaptic plasticity in the medial prefrontal cortex (mPFC) is occluded in rats vulnerable to CMS, likely reflecting differential expression of AMPA receptors. Interestingly, such difference is not observed when rats are acutely treated with sub-anesthetic ketamine, possibly through the recruitment of dopaminergic nuclei such as the ventral tegmental area. In addition, by applying the synaptic activity sensor SynaptoZip in vivo, we found that chronic stress unbalances the synaptic drive from the infralimbic and prelimbic subregions of the mPFC toward the basolateral amygdala, and that this effect is counteracted by ketamine. Our results provide novel insights into the neurophysiological mechanisms behind the expression of vulnerability to stress, as well as behind the antidepressant action of ketamine.

Lamanna, J., Isotti, F., Ferro, M., Spadini, S., Racchetti, G., Musazzi, L., et al. (2022). Occlusion of dopamine-dependent synaptic plasticity in the prefrontal cortex mediates the expression of depressive-like behavior and is modulated by ketamine. SCIENTIFIC REPORTS, 12(1 (December 2022)) [10.1038/s41598-022-14694-w].

Occlusion of dopamine-dependent synaptic plasticity in the prefrontal cortex mediates the expression of depressive-like behavior and is modulated by ketamine

Musazzi L.;
2022

Abstract

Unpredictable chronic mild stress (CMS) is among the most popular protocols used to induce depressive-like behaviors such as anhedonia in rats. Differences in CMS protocols often result in variable degree of vulnerability, and the mechanisms behind stress resilience are of great interest in neuroscience due to their involvement in the development of psychiatric disorders, including major depressive disorder. Expression of depressive-like behaviors is likely driven by long-term alterations in the corticolimbic system and by downregulation of dopamine (DA) signaling. Although we have a deep knowledge about the dynamics of tonic and phasic DA release in encoding incentive salience and in response to acute/chronic stress, its modulatory action on cortical synaptic plasticity and the following implications on animal behavior remain elusive. Here, we show that the expression of DA-dependent synaptic plasticity in the medial prefrontal cortex (mPFC) is occluded in rats vulnerable to CMS, likely reflecting differential expression of AMPA receptors. Interestingly, such difference is not observed when rats are acutely treated with sub-anesthetic ketamine, possibly through the recruitment of dopaminergic nuclei such as the ventral tegmental area. In addition, by applying the synaptic activity sensor SynaptoZip in vivo, we found that chronic stress unbalances the synaptic drive from the infralimbic and prelimbic subregions of the mPFC toward the basolateral amygdala, and that this effect is counteracted by ketamine. Our results provide novel insights into the neurophysiological mechanisms behind the expression of vulnerability to stress, as well as behind the antidepressant action of ketamine.
Si
Articolo in rivista - Articolo scientifico
Scientifica
Animals; Dopamine; Humans; Neuronal Plasticity; Prefrontal Cortex; Rats; Depressive Disorder, Major; Ketamine
English
Lamanna, J., Isotti, F., Ferro, M., Spadini, S., Racchetti, G., Musazzi, L., et al. (2022). Occlusion of dopamine-dependent synaptic plasticity in the prefrontal cortex mediates the expression of depressive-like behavior and is modulated by ketamine. SCIENTIFIC REPORTS, 12(1 (December 2022)) [10.1038/s41598-022-14694-w].
Lamanna, J; Isotti, F; Ferro, M; Spadini, S; Racchetti, G; Musazzi, L; Malgaroli, A
File in questo prodotto:
File Dimensione Formato  
Lamanna-2022-SciRep-VoR.pdf

accesso aperto

Descrizione: Article
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 8.04 MB
Formato Adobe PDF
8.04 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/392214
Citazioni
  • Scopus 0
  • ???jsp.display-item.citation.isi??? ND
Social impact