Modulation Of Ltp Induction


Iso + H7

BOX 5 Neuromodulation of LTP induction. (A) Modulation of LTP induction by the beta-adrenergic agonist Isoproterenol (ISO). Activity-dependent P-adrenergic modulation of low-frequency stimulation-induced LTP in the hippocampus CA1 region. (A) In control experiments (no ISO), 3 minutes of 5-Hz stimulation (delivered at time = 0, open symbols, n = 26) had no lasting effect on synaptic transmission (45 minutes after 5-Hz stimulation, fEPSPs were not significantly different from pre-5-Hz baseline, t(25) = 1.01). However, 3 minutes of 5-Hz stimulation delivered at the end of a 10-minute application of 1.0 mM ISO (indicated by the bar) induced LTP (closed symbols, p < .01 compared with baseline). The traces are fEPSPs recorded during baseline and 45 minutes after 5-Hz stimulation in the presence and absence (control) of ISO. Calibration bars are 2.0 mV and 5.0 ms. Reproduced from Thomas, Moody, Makhinson, and O'Dell (33).

(B) One potential mechanism for neuromodulation is regulation of back-propagating action potentials in CA1 dendrites. The data shown illustrate amplification of dendritic action potentials by isoproterenol (a) and its susceptibility to inhibition by the protein kinase inhibitor H7 (b). The traces shown are from dendritic patch-clamp recordings from hippocampal pyramidal neurons. Muscarinic agonist (carbachol, c) and the dopamine receptor agonist 8-Cl-PB also can give various degrees of action-potentail modulation as well. (a) Bath application of 1 pM isoproterenol resulted in a 104% increase in amplitude, from 41 mV(Pre) to 84 mV, of an antidromically initiated action potential recorded 220 pm from the soma. (Wash-out of isoproterenol is indicated by wash). With a second application of isoproterenol (dark arrow labeled 'Iso'), the amplitude again increased twofold to 80 mV. (b) In a different recording (300 pM H-7), a generic kinase inhibitor was included in the control saline during the wash-out of isoproterenol. The subsequent second application of isoproterenol failed to lead to a second increase in amplitude (dark arrow labeled 'Iso + H7'). (c) In a similar recording, 1 pM carbachol increased the action potential amplitude by 81%, from 27 to 60 mV. In the carbachol experiments, cells were held hyperpolarized to -80 mV to remove Na+ channel inactivation. (d) One of the 6 out of 10 recordings where 6-Cl-PB led to an increase in amplitude. In a recording 220 pm from the soma, 10 pM 6-Cl-PB increased dendritic action potential amplitude by 26%, from 21 to 26.5 mV. The cells were held at -70 mV in all 6-Cl-PB experiments. Adapted from Johnston, Hoffman, Colbert, and Magee (15).


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