Figure 1.
Muscarinic effects in the absence of background activity. A, Firing of a layer 5 pyramidal neuron in forelimb motor cortex before (Control) and after (Oxo-M) application of Oxo-M in response to a DC step. In this case, muscarinic activation reversed spike frequency adaptation, causing the instantaneous frequency to increase rather than decrease over the course of the spike train. (In all figures, when data from control and Oxo-M conditions are plotted together, the former are in black, and the latter are in gray.) B, Muscarinic receptor activation increased the average number of spikes produced by a 1 s DC step consistently over a wide range of amplitudes (top panel). On average, it also reduced, but did not reverse, spike frequency adaptation. Plotted in the bottom panel are the instantaneous spike frequencies produced by a 200 pA current step as a function of spike interval number, normalized to the frequency for the first interval (n = 20 for both graphs). C, Muscarinic receptor activation replaced the burst afterhyperpolarization with a burst afterdepolarization. The size of the afterdepolarization varied with the intensity of the burst and could give rise to prolonged spike firing. Shown is the response of one neuron in the presence of Oxo-M to current injections of three different amplitudes (bottom traces). D, In some neurons, the afterdepolarization produced persistent graded activity. The top trace (Vm) shows spike firing induced by the current injections of the middle trace (I). Note that the instantaneous firing rate (FR) shown in the bottom trace could be ramped up or down in a controlled, step-like manner. Calibration: 25 mV, 100 pA; 6 Hz vertical; 10 s horizontal.