Electrophysiologically identified presynaptic mechanisms underlying amylinergic modulation of area postrema neuronal excitability in rat brain slices

• Published in: Brain research 2013-02, Vol.1494, p.9-16
• Main Authors: Fukuda, Takeshi, Hirai, Yoshiyuki, Maezawa, Hitoshi, Kitagawa, Yoshimasa, Funahashi, Makoto
• Format: Article
• Language: English
• Subjects: Action potential; action potentials; alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; Amylin; Animals; antagonists; Area postrema; Area Postrema - cytology; Area Postrema - metabolism; Beta cells; Biological and medical sciences; Brain slice; Brain slice preparation; Brain stem; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cyclic Nucleotide-Gated Cation Channels - metabolism; energy; Energy balance; Excitability; Excitatory postsynaptic potentials; Feeding behavior; Food intake; Fundamental and applied biological sciences. Psychology; glutamic acid; Glutamic Acid - metabolism; Glutamic acid receptors; homeostasis; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; In Vitro Techniques; Insulin; Ion currents; Islet Amyloid Polypeptide - metabolism; islets of Langerhans; Membrane Potentials - physiology; Nerve Tissue Proteins - metabolism; Neurology; Neuromodulation; Neurons; Obesity; Pancreas; Patch-clamp; Patch-Clamp Techniques; Potassium Channels - metabolism; Presynaptic Terminals - metabolism; Rat; Rats; Rats, Sprague-Dawley; receptors; Synaptic Transmission - physiology; Tissue Distribution; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2012.11.051

Abstract Amylin, which is co-secreted together with insulin by pancreatic beta cells, is considered to be an important peptide hormone involved in the control of feeding behavior and energy homeostasis. Although the area postrema has been implicated to be a primary target of amylin, there are no studies of the mechanisms by which amylin may alter the excitability of area postrema neurons. To investigate the mechanism for amylinergic modulation of neuronal excitability, we performed perforated patch-clamp recordings from area postrema neurons in rat brainstem slices. Amylin-induced changes in excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents) and changes in the amplitude distribution of mEPSCs, were found in cells not displaying the hyperpolarization-activated cation current ( I h ). Area postrema cells displaying I h did not respond to amylin application. Inhibitory responses to amylin were never encountered. Bath application of CNQX (AMPA type glutamate receptor antagonist) abolished the effects of amylin. Depolarization of cells during amylin application was sufficient at 1 μM to cause action potential discharge by responding cells. We conclude that amylin receptors are located mostly on presynaptic glutamatergic terminals connecting to the area postrema neurons not displaying I h and amylin concentrations can increase glutamate release enough to cause cell firing. Modulation of amylinergic activity may offer a novel target to influence food intake and obesity.