Positive Modulation of AMPA Receptors Increases Neurotrophin Expression by Hippocampal and Cortical Neurons

• DOI: 10.1523/jneurosci.20-01-00008.2000
• Publication Date: 2018-04-04T20:40:32Z
• Authors: Julie C. Lauterborn; Gary Lynch; Peter Vanderklish; Amy Arai; Christine M. Gall
• Keywords: Neurotrophin-3

This study investigated whether positive modulators of AMPA-type glutamate receptors influence neurotrophin expression by forebrain neurons. Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA protein levels in cultured rat entorhinal/hippocampal slices. Acute effects were dose dependent over range which drug synchronous neuronal discharges; threshold concentrations for acute responses had large on content when applied 3 d. Comparable results obtained a second, structurally distinct CX546. Ampakine-induced upregulation was broadly suppressed AMPA, but not NMDA, receptor antagonists reducing transmitter release. Antagonism L-type voltage-sensitive calcium channels blocked induction entorhinal cortex hippocampus. Prolonged infusions suprathreshold produced peak BDNF at 12 hr return to baseline 48 hr. In contrast, remained elevated throughout incubation drug. Nerve growth also ampakines much more rapid control during chronic administration. Finally, intraperitoneal injections CX546 hippocampal aged rats middle-aged mice. The present provide evidence regional differences mechanisms via activity regulates expression. Moreover, these data establish that changes synaptic potency produce sufficient network level physiological inducing genes, indicate response becomes refractory prolonged exposure, raise possibility using AMPA regulate brain.