Tonic glutamate in CA1 of aging rats correlates with phasic glutamate dysregulation during seizure.

Objective: Characterize glutamate neurotransmission in the hippocampus of awake-behaving rodents during focal seizures in a model of aging.

Methods: We used enzyme-based ceramic microelectrode array technology to measure in vivo extracellular tonic glutamate levels and real-time phasic glutamate release and clearance events in the hippocampus of awake Fischer 344 rats. Local application of 4-aminopyridine (4-AP) into the CA1 region was used to induce focal motor seizures in different animal age groups representing young, late-middle aged and elderly humans.

Resting glutamate levels and rapid glutamate transients in the prefrontal cortex of the Flinders Sensitive Line rat: a genetic rodent model of depression.

Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (~30%) and slow onset of action (2-4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2 Hz) and high spatial (15 × 333 μm) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression.

Real-time glutamate measurements in the putamen of awake rhesus monkeys using an enzyme-based human microelectrode array prototype.

Commonly used for research studies in the central nervous system, microdialysis has revealed a link between dysregulation of the excitatory neurotransmitter glutamate and ischemia and seizure, however limitations like slow temporal resolution have stalled the advancement of microdialysis as a diagnostic tool. We have developed and extensively characterized an enzyme-based microelectrode array technology for second-by-second in vivo amperometric measurements of glutamate in the mammalian CNS. The current studies demonstrated the ability of a human microelectrode array prototype (Spencer-Gerhardt-2 (SG-2)) to measure tonic and phasic glutamate neurotransmission in the putamen of unanesthetized non-human primates.

Age-related changes in glutamate release in the CA3 and dentate gyrus of the rat hippocampus.

The present studies employed a novel microelectrode array recording technology to study glutamate release and uptake in the dentate gyrus, CA3 and CA1 hippocampal subregions in anesthetized young, late-middle aged and aged male Fischer 344 rats. The mossy fiber terminals in CA3 showed a significantly decreased amount of KCl-evoked glutamate release in aged rats compared to both young and late-middle-aged rats. Significantly more KCl-evoked glutamate release was seen from perforant path terminals in the DG of late-middle-aged rats compared young and aged rats.

Amperometric measures of age-related changes in glutamate regulation in the cortex of rhesus monkeys.

l-glutamate (glutamate) is the principal excitatory neurotransmitter of the central nervous system and is involved in altered neural function during aging and in neurodegenerative diseases. Relatively little is known about the mechanisms of glutamate signaling in the primate brain, in part, because there is an absence of a method capable of rapidly measuring glutamate in either a non-clinical or a clinical setting. We have addressed this paucity of information by measuring extracellular glutamate at 1 Hz in the pre-motor and motor cortices of young, middle-aged, and aged monkeys using a minimally invasive amperometric recording method.