Figure 5.

Inverted-U dose-response with changing NE levels. (A) When NE levels were varied from low to high, we saw changes in the firing rate of working memory neurons that were consistent with those found experimentally. When NE levels were low (left), α2A receptors were only weakly activated causing a decrease in the strength of recurrent connections within a column and, ultimately, a degradation of working memory as can be seen by the low firing rates in both preferred (column 1) and non-preferred (column 2) neurons. The firing rates of preferred direction neurons vs. non-preferred direction neurons during the delay period were significantly different since non-preferred direction neurons showed no response at all (p < 10⁻⁸; t-test). When NE levels were high (right), all inputs to neurons in the PFC network were partially blocked due to α1 receptor stimulation, leading to a decrease firing rate to both preferred and non-preferred neurons (p > 0.05; t-test). When NE levels were optimal, preferred neuron firing rates were higher than non-preferred neurons as is characteristic in successful working memory traces (p < 10⁻⁸; t-test). Note that the optimal and high NE conditions are the same as in Figure 4A due to the fact that identical neuromodulatory changes in the network are imposed in each of these states. (B) Experimental results from Birnbaum et al. (2004); Wang et al. (2007); Arnsten (2011) showing a similar inverted-U response with varying NE levels.