In vivo co‐ordinated interactions between inhibitory systems to control glutamate‐mediated hippocampal excitability

• Published in: Journal of neurochemistry 2005-11, Vol.95 (3), p.651-661
• Main Authors: Rodríguez, M. J., Robledo, P., Andrade, C., Mahy, N.
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - physiology; adenosine; Adenosine - metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - toxicity; Animals; Biochemistry; Biological and medical sciences; Brain research; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Denervation; Dizocilpine Maleate - metabolism; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Agonists - toxicity; Excitatory Amino Acid Antagonists - metabolism; Excitatory Amino Acid Antagonists - pharmacology; excitotoxicity; Fundamental and applied biological sciences. Psychology; GABA; GABA Agonists - metabolism; GABA Agonists - pharmacology; gamma-Aminobutyric Acid - metabolism; glutamate; Glutamic Acid - metabolism; Hipocamp (Cervell); Hippocampus (Brain); Hippocampus - physiology; Male; Medical sciences; microdialysis; Muscarinic Antagonists - metabolism; Muscarinic Antagonists - pharmacology; Muscimol - metabolism; Muscimol - pharmacology; Neural Inhibition - physiology; Neural transmission; Neurology; Neurotransmissió; Neurotransmitter receptors; Quinuclidinyl Benzilate - metabolism; Quinuclidinyl Benzilate - pharmacology; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors de neurotransmissors; Rodents; Septal Nuclei - physiology; Synaptic Transmission - physiology; taurine; Taurine - metabolism; Tritium; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03394.x

We present an overview of the long‐term adaptation of hippocampal neurotransmission to cholinergic and GABAergic deafferentation caused by excitotoxic lesion of the medial septum. Two months after septal microinjection of 2.7 nmol α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA), a 220% increase of GABAA receptor labelling in the hippocampal CA3 and the hilus was shown, and also changes in hippocampal neurotransmission characterised by in vivo microdialysis and HPLC. Basal amino acid and purine extracellular levels were studied in control and lesioned rats. In vivo effects of 100 mm KCl perfusion and adenosine A1 receptor blockade with 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX) on their release were also investigated. In lesioned animals GABA, glutamate and glutamine basal levels were decreased and taurine, adenosine and uric acid levels increased. A similar response to KCl infusion occurred in both groups except for GABA and glutamate, which release decreased in lesioned rats. Only in lesioned rats, DPCPX increased GABA basal level and KCl‐induced glutamate release, and decreased glutamate turnover. Our results evidence that an excitotoxic septal lesion leads to increased hippocampal GABAA receptors and decreased glutamate neurotransmission. In this situation, a co‐ordinated response of hippocampal retaliatory systems takes place to control neuron excitability.