title: Early stress prevents the potentiation of muscarinic excitation by calcium release in adult prefrontal cortex.
abstract: BACKGROUND
  The experience of early stress contributes to the etiology of several psychiatric disorders and can lead to lasting deficits in working memory and attention. These executive functions require activation of the prefrontal cortex (PFC) by muscarinic M1 acetylcholine (ACh) receptors. Such Gαq-protein coupled receptors trigger the release of calcium (Ca(2+)) from internal stores and elicit prolonged neuronal excitation.
  
  
  METHODS
  In brain slices of rat PFC, we employed multiphoton imaging simultaneously with whole-cell electrophysiological recordings to examine potential interactions between ACh-induced Ca(2+) release and excitatory currents in adulthood, across postnatal development, and following the early stress of repeated maternal separation, a rodent model for depression. We also investigated developmental changes in related genes in these groups.
  
  
  RESULTS
  Acetylcholine-induced Ca(2+) release potentiates ACh-elicited excitatory currents. In the healthy PFC, this potentiation of muscarinic excitation emerges in young adulthood, when executive function typically reaches maturity. However, the developmental consolidation of muscarinic ACh signaling is abolished in adults with a history of early stress, where ACh responses retain an adolescent phenotype. In prefrontal cortex, these rats show a disruption in the expression of multiple developmentally regulated genes associated with Gαq and Ca(2+) signaling. Pharmacologic and ionic manipulations reveal that the enhancement of muscarinic excitation in the healthy adult PFC arises via the electrogenic process of sodium/Ca(2+) exchange.
  
  
  CONCLUSIONS
  This work illustrates a long-lasting disruption in ACh-mediated cortical excitation following early stress and raises the possibility that such cellular mechanisms may disrupt the maturation of executive function.
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors: Éliane
authors: É
authors: Proulx
authors: Tata Institute of Fundamental Research, Mumbai, India.
authors: Deepika
authors: D
authors: Suri
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Heart and Stroke/Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, Toronto, Ontario, Canada.
authors: Scott P
authors: SP
authors: Heximer
authors: Tata Institute of Fundamental Research, Mumbai, India.
authors: Vidita A
authors: VA
authors: Vaidya
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada. Electronic address: evelyn.lambe@utoronto.ca.
authors: Evelyn K
authors: EK
authors: Lambe
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003863:Depression; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology*; D046509:Tissue Culture Techniques
chemical_list: D000109:Acetylcholine; D002118:Calcium
keywords: Acetylcholine; calcium imaging; development; maternal separation; muscarinic M1 receptor; slice electrophysiology