Long-term potentiation (LTP) in vivo - test for nootropica

Fields of research:

Involvement of transmitter receptors and second messengers in mechanisms of long-term potentiation (artifical model for basic mechanisms of memory formation)

Original description of multiple phases of LTP in 1987

LTP experiments conducted on awake, freely moving rats

Methods of research:

Surgery:

To record monosynaptic evoked field potentials and to induce LTP in the dentate gyrus after stimulation of the entorhinal-dentate pathway, Wistar rats aged 8 weeks are chronically implanted with a bipolar stimulation electrode in the ipsilateral perforant pathway (angular bundle) and a monopolar recording electrode in the dorsal blade of the ipsilateral dentate gyrus. The electrodes are made from polyurethane-coated stainless steel wires with a diameter of 125 µm. The animals were deeply anesthetized with pentobarbital and mounted on a  stereotaxic instrument with  1 mm below bregma. Electrodes are placed under direct electrophysiological guidance following stereotaxic coordinates: anteroposterior (AP), 2.8 mm; lateral (L), 1.8 mm; and AP, 6.8 mm; L, 4.1 mm. Animals are allowed to recover for at least 10 d after surgery.

Electrophysiological recording:

For electrophysiological recording, animals are connected to a stimulator and an AC-coupled amplifier (frequency range of 2 Hz to 10 kHz) through flexible, shielded cable and a swivel, thus allowing free movement. To elicit evoked potentials, a series of eight biphasic square wave impulses with a duration of 100 µsec/half-wave is generated with a frequency of 0.2 Hz. The field potentials are digitised with a resolution of 100 µsec, averaged, and stored on a hard disk. The slope function of the field EPSP (fEPSP) and population spike (PS) amplitude are automatically calculated as the steepest 400 µsec segment of the initial potential upstroke and the peak to peak difference, respectively. Non-decremental LTP is induced by stimulating the ipsilateral perforant pathway with 20 trains of impulses. Each train consisted of 15 pulses having the same duration as the test pulse. The frequency within the train was 200 Hz for high-frequency stimulation or 0.2 Hz for low-frequency stimulation, and the distance between trains is 5 sec. For induction of decremental LTP, animals receive only two stimulus trains. 

For further information please contact:

Prof. Klaus Reymann
phone: +49(391)6263437
fax: +49(391)6263438
reymann@fan-neuroscience.com  
 

Dr. Petra Henrich-Noack
phone: +49(391)6263794 or 6117204
noack@ifn-magdeburg.de 

Recent publications:

Riedel, G., Casabona, G., and Reymann, K.G.: Inhibition of long-term potentiation in the dentate gyrus of freely moving rats by the metabotropic glutamate receptor antagonist MCPG. J. Neurosci., 1995, 15, 87-98

Manahan-Vaughan, D., Braunewell K.H. and Reymann, K.G.: Subtype-specific involvement of metabotropic glutamate receptors in two forms of long-term potentiation in the dentate gyrus of freely moving rats. Neuroscience, 1998, 86, 709-721

Seidenbecher, T., Reymann, K.G., and Balschun, D.: A post-tetanic time window for the reinforcement of LTP by appetitive and aversive stimuli. Proc. Natl. Acad. Sci. 1997, 94, 1494-1499

Balschun, D., Manahan-Vaughan, D., Wagner, T., Behnisch, T., Reymann, K.G, Wetzel, W.: A specific role for mGluRs in hippocampal LTP and hippocampus-dependent spatial learning. Learning and Memory, 1999, 6, 138-152