title: Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery.
abstract: Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of IL layer V pyramidal neurons from male Sprague-Dawley rats subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over extension of proximal dendritic arbors and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry reestablishment may underlie elements of recovery. Accordingly, we believe that pharmacological treatments targeted at preventing dendritic retraction and spine loss or encouraging circuitry re-establishment and stabilization may be advantageous in the prevention and treatment of mood and anxiety disorders.
authors.affiliation: Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Goldwater
authors.forename: C
authors.initials: C
authors.lastname: Pavlides
authors.forename: R G
authors.initials: RG
authors.lastname: Hunter
authors.forename: E B
authors.initials: EB
authors.lastname: Bloss
authors.forename: P R
authors.initials: PR
authors.lastname: Hof
authors.forename: B S
authors.initials: BS
authors.lastname: McEwen
authors.forename: J H
authors.initials: JH
authors.lastname: Morrison
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D015430:Weight Gain
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine