Abstract
Oscillations in hippocampal neuronal networks in the gamma frequency band have been implicated in various cognitive tasks and we showed previously that aging reduces the power of such oscillations. Here, using submerged hippocampal slices allowing simultaneous electrophysiological recordings and imaging, we studied the correlation between the kainate-evoked gamma oscillation and mitochondrial activity, as monitored by rhodamine 123. We show that the initiation of kainate-evoked gamma oscillations induces mitochondrial depolarization, indicating a metabolic response. Aging had an opposite effect on these parameters: while depressing the gamma oscillation strength, it increases mitochondrial depolarization. Also, in the aged neurons, kainate induced significantly larger Ca2+ signals. In younger slices, acute mitochondrial depolarization induced by low concentrations of mitochondrial protonophores strongly, but reversibly, inhibits gamma oscillations. These data indicating that the complex network activity required by the maintenance of gamma activity is susceptible to changes and modulations in mitochondrial status.
Highlights
Normal brain aging is characterized by a mild decline in cognitive performance (Hedden and Gabrieli, 2004), that includes modules dependent on hippocampal function, as shown both in humans and animals (Erickson and Barnes, 2003)
Our results show that the initiation of the kainate-induced gamma oscillation activity induced an increased Rhodamine 123 (R123) fluorescence signal that is a functional marker for mitochondrial depolarization (Xiong et al, 2002, 2004) resulting from increased levels of metabolic activity
To correlate with the population nature of the field recordings that measured oscillatory activity, our R123 fluorescence measurements were recorded from the whole field of view, rather than from individual cells
Summary
Normal brain aging is characterized by a mild decline in cognitive performance (Hedden and Gabrieli, 2004), that includes modules dependent on hippocampal function, as shown both in humans and animals (Erickson and Barnes, 2003). While the pyramidal cells fire during the gamma activity at 1–3 Hz, the fast-spiking interneurons fire action potentials up to 40 Hz in a phase-locked manner (Hájos et al, 2004). Such rates of firing, sustained over longer periods of time during the neurotransmitter-evoked gamma activity, are likely to impose significant metabolic demands (Huchzermeyer et al, 2008; Lu et al, 2011a). From a metabolic standpoint, by a reduction in the homeostatic reserve, defined as the neuronal capacity to respond effectively to metabolic stressors (Toescu, 2005; Toescu and Vreugdenhil, 2010), and underpinned by mitochondrial dysfunction (Kann and Kovács, 2007; Xiong et al, 2002) and alterations in Ca2ϩ homeostasis (Toescu et al, 2004)
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