Signaling Pathways Relevant to Cognition-Enhancing Drug Targets

  • Caroline Ménard
  • Pierrette Gaudreau
  • Rémi QuirionEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 228)


Aging is generally associated with a certain cognitive decline. However, individual differences exist. While age-related memory deficits can be observed in humans and rodents in the absence of pathological conditions, some individuals maintain intact cognitive functions up to an advanced age. The mechanisms underlying learning and memory processes involve the recruitment of multiple signaling pathways and gene expression, leading to adaptative neuronal plasticity and long-lasting changes in brain circuitry. This chapter summarizes the current understanding of how these signaling cascades could be modulated by cognition-enhancing agents favoring memory formation and successful aging. It focuses on data obtained in rodents, particularly in the rat as it is the most common animal model studied in this field. First, we will discuss the role of the excitatory neurotransmitter glutamate and its receptors, downstream signaling effectors [e.g., calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase C (PKC), extracellular signal-regulated kinases (ERK), mammalian target of rapamycin (mTOR), cAMP response element-binding protein (CREB)], associated immediate early gene (e.g., Homer 1a, Arc and Zif268), and growth factors [insulin-like growth factors (IGFs) and brain-derived neurotrophic factor (BDNF)] in synaptic plasticity and memory formation. Second, the impact of the cholinergic system and related modulators on memory will be briefly reviewed. Finally, since dynorphin neuropeptides have recently been associated with memory impairments in aging, it is proposed as an attractive target to develop novel cognition-enhancing agents.


Aging Memory Synaptic plasticity Glutamate Acetylcholine Dynorphin 



This research was supported by grants from the Canadian Institutes of Health Research (CIHR) to R.Q. and the Quebec Network for Research on Aging (a network funded by the Fonds de recherche du Québec—Santé) to P.G. C.M. was the recipient of a postdoctoral fellowship from CIHR.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Caroline Ménard
    • 1
    • 2
    • 3
    • 4
  • Pierrette Gaudreau
    • 3
    • 4
  • Rémi Quirion
    • 1
    • 2
    Email author
  1. 1.Douglas Mental Health University InstituteMcGill UniversityMontrealCanada
  2. 2.Department of PsychiatryMcGill UniversityMontrealCanada
  3. 3.Centre Hospitalier de l’Université de Montréal Research CenterMontrealCanada
  4. 4.Department of MedicineUniversity of MontrealMontrealCanada

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