Simultaneous recording of hippocampal oxygen and glucose in real time using constant potential amperometry in the freely-moving rat

Abstract

h i g h l i g h t sWe show that average concentrations of hippocampal oxygen and glucose are 100.26 ± 5.76 M and 0.60 ± 0.06 mM respectively. We show that there are uncoupled changes in oxygen and glucose during neuronal activation. Anaesthesia and carbonic anhydrase inhibition both significantly increase hippocampal oxygen. Anaesthesia, dimethyl sulfoxide administration and carbonic anhydrase inhibition significantly increase hippocampal glucose. We show that changes in hippocampal metabolism can be detected in real time using constant potential amperometry. a r t i c l e i n f o t r a c tAmperometric sensors for oxygen and glucose allow for real time recording from the brain in freelymoving animals. These sensors have been used to detect activity-and drug-induced changes in metabolism in a number of brain regions but little attention has been given over to the hippocampus despite its importance in cognition and disease. Sensors for oxygen and glucose were co-implanted into the hippocampus and allowed to record for several days. Baseline recordings show that basal concentrations of hippocampal oxygen and glucose are 100.26 ± 5.76 M and 0.60 ± 0.06 mM respectively. Furthermore, stress-induced changes in neural activity have been shown to significantly alter concentrations of both analytes in the hippocampus. Administration of O 2 gas to the animals' snouts results in significant increases in hippocampal oxygen and glucose and administration of N 2 gas results in a significant decrease in hippocampal oxygen. Chloral hydrate-induced anaesthesia causes a significant increase in hippocampal oxygen whereas treatment with the carbonic anhydrase inhibitor acetazolamide significantly increases hippocampal oxygen and glucose. These findings provide real time electrochemical data for the hippocampus which has been previously impossible with traditional methods such as microdialysis or ex vivo analysis. As such, these sensors provide a window into hippocampal function which can be used in conjunction with behavioural and pharmacological interventions to further elucidate the functions and mechanisms of action of the hippocampus in normal and disease states.

Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

“…Interestingly, reducing extracellular glucose concentration is thought be one of the most important points for reproducing the effects of ketogenic diet in this approach. Synaptic transmission in hippocampal slices from ketogenic diet-fed rodents were not different from slices from control diet-fed rodents when extracellular glucose concentration in artificial cerebrospinal fluid is standard in all three reports [however, evidence is mounting that this standard glucose concentration for acute brain slices is higher than physiological brain glucose levels (Shram et al, 1997; Lowry and Fillenz, 2001; Kealy et al, 2013)]. Reduced glucose reveals the difference between ketogenic diet- and control diet-fed animals in two of these studies (Bough et al, 2006; Kawamura et al, 2014), which parallels the finding that the anticonvulsant effect of the ketogenic diet is correlated with plasma glucose levels (Mantis et al, 2004).…”

Rapid Physiological Fluctuations in Nucleus Accumbens Oxygen Levels Induced by Arousing Stimuli: Relationships with Changes in Brain Glucose and Metabolic Neural Activation

“…Although the principles of voltammetric oxygen detection in brain tissue have a long history (Davies and Brink, 1942; Davies and Bronk, 1957; Clark et al, 1958) and the development of small oxygen sensors coupled with high-speed amperometry (Lowry et al, 1997; Bolger and Lowry, 2005; Bolger et al, 2011; Francois et al, 2012; Kealy et al, 2013; Lyons et al, 2016) or cyclic voltammetry (Wang and Venton, 2016) have made it possible to evaluate changes in oxygen levels in discrete brain areas with high temporal resolution, data on physiological fluctuations in brain oxygen levels are very limited.…”

Characterisation of a Platinum‐based Electrochemical Biosensor for Real‐time Neurochemical Analysis of Choline

“…Once surgical anaesthesia was established animals were placed in a stereotaxic frame and the sensors implanted following a previously described procedure [12]. The level of anaesthesia was checked regularly (pedal withdrawal reflex).…”