Prolonged Ca2+ -dependent afterhyperpolarization in hippocampal neurons of aged rats. Science
ABSTRACT The possibility that calcium is elevated in brain neurons during aging was examined by quantifying afterhyperpolarizations induced by spike bursts in CAl neurons of hippocampal slices from young and aged rats. The afterhyperpolarizations result from Ca2+-dependent K+ conductance increases and are blocked in medium low in Ca2+ and prolonged in medium high in Ca2+. The afterhyperpolarization and associated conductance increases were considerably prolonged in cells from aged rats, although inhibitory postsynaptic potentials did not differ with age. Since elevated intracellular Ca2+ can exert deleterious effects on neurons, the data suggest that altered Ca2+ homeostasis may play a significant role in normal brain aging.
- SourceAvailable from: Valerio Rizzo
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- "intrinsic cellular properties of neurons (Driver et al., 2004; Chang et al., 2005; Wilson et al., 2005; Disterhoft and Oh, 2007; Luebke and Chang, 2007; Matthews et al., 2009). Investigations on the central nervous system (CNS) structures with crucial roles in cognitive processing have shown age-related alteration of intrinsic neuronal excitability (Landfield and Pitler, 1984; Disterhoft and Oh, 2007; Matthews et al., 2009; Oh et al., 2010; Wang et al., 2011). Consistent with this idea, aging neurons have been observed undergoing structural changes such as decreases in soma size (de Brabander et al., 1998; Wong et al., 2000; Figure 1), loss/regression of dendrites and loss of dendritic spines (Jacobs et al., 1997; Peters et al., 1998; Page et al., 2002; Duan et al., 2003; Figure 1), loss of synapses (Chen et al., 1995; Wong et al., 1998; Figure 1), alterations in neurotransmitter receptors (Post-Munson et al., 1994; Rosene and Nicholson, 1999; Figure 1) and/or decreased response to neurotransmitters (Fieber et al., 2010; Akhmedov et al., 2013; Kempsell and Fieber, 2014). "
ABSTRACT: Several studies using vertebrate and invertebrate animal models have shown aging associated changes in brain function. Importantly, changes in soma size, loss or regression of dendrites and dendritic spines and alterations in the expression of neurotransmitter receptors in specific neurons were described. Despite this understanding, how aging impacts intrinsic properties of individual neurons or circuits that govern a defined behavior is yet to be determined. Here we discuss current understanding of specific electrophysiological changes in individual neurons and circuits during aging.Frontiers in Aging Neuroscience 02/2015; 6. DOI:10.3389/fnagi.2014.00337 · 2.84 Impact Factor
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- "), is enhanced in aging animals (Kumar & Foster, 2002; Landfield & Pitler, 1984; Moyer & Disterhoft, 1994; Moyer, Thompson, Black, & Disterhoft, 1992). In aged animals, an enhanced sI AHP is correlated with an enhanced sAHP and impaired learning ability (Power, Wu, Sametsky, Oh, & Disterhoft, 2002). "
ABSTRACT: "Use it or lose it" is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity - a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability - this can prevent or provide treatment for cognitive decline not only in patients with clinical disorders but also in the aging population.Neurobiology of Learning and Memory 07/2013; 105. DOI:10.1016/j.nlm.2013.07.008 · 4.04 Impact Factor
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- "This would suggest that DMV neuronal excitability is not only decreased in adult rats (or the obesity associated with adulthood and ageing in rats), but that these effects are also reversible following RYGB. Decreased neuronal excitability often accompanies ageing due, in part, to intracellular calcium dysregulation and increased action potential after-hyperpolarization (Landfield & Pitler, 1984; Foster & Kumar, 2002; Nikoletopoulou & Tavernarakis, 2012), similar to that observed in the present study. Clearly, it remains to be determined whether the observed RYGB-dependent restoration of DMV neuronal excitability is due to weight loss and decreased adiposity, or whether it is due to reversal of ageing-induced calcium dysregulation. "
ABSTRACT: Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibers, although the effects of DIO on central vagal neurones have never been investigated. The aims of this study were to investigate whether high-fat diet (HFD)-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight-loss induced by Roux-en-Y gastric bypass surgery (RYGB). Whole cell patch clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. DMV neurones from rats exposed to HFD for 12-14 weeks, were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1). RYGB reversed all of these DIO-induced effects. DIO also affected the morphological properties of DMV neurons, increasing their dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium dependent potassium current. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal neuronal health in the brain by reversing some effects of chronic high fat diet. Vago-vagal neurocircuits appear to remain open to modulation and adaptation throughout life and understanding these mechanisms may help to develop novel interventions to alleviate environmental (e.g. dietary) ailments.The Journal of Physiology 03/2013; 591(9). DOI:10.1113/jphysiol.2012.249268 · 4.54 Impact Factor