2011b). For a “glutamatergic feedback cascade” model to hold, we need to explain an effect on inhibitory selleckchem neurons that is generally stronger and more consistent than the effect observed in the population of cells that drives them. One solution is to propose amplifying local connectivity and/or a specific feedback-receptive sub-circuit and to then seek evidence of the necessary supporting neural architectures. An alternate (not in fact mutually exclusive) explanation envisages post-synaptic

amplification of the feedback signal by a neuromodulatory system acting through specific and strong receptor expression by PV neurons. Such a model is consistent with the strong Inhibitors,research,lifescience,medical expression of m1 AChRs by PV neurons that we report here. But we also report strong expression by non-PV neurons, many of which are likely to be excitatory. If many excitatory neurons show weak and inconsistent effects of attention and many inhibitory neurons show strong and consistent effects of attention – can this possibly be mediated by ACh acting via a receptor type (m1) that is, expressed in both cell classes? Anderson Inhibitors,research,lifescience,medical et al. (2011a) report that there is a population of putatively excitatory neurons that do show strong modulation of firing rate by attention – neurons that fire their spikes in bursts. If ACh is the

mediator of attention-related effects in extrastriate Inhibitors,research,lifescience,medical cortex, then one prediction from the current data would be that both narrow-spiking neurons and broad-spiking neurons that tend to fire their spikes in bursts should be sensitive to m1 AChR-selective

agonists and antagonists while those that do not fire Inhibitors,research,lifescience,medical spikes in burst will be insensitive to these same pharmacological agents. Downstream targets for m1 AChR-mediated modulation It could also be that the downstream targets for m1 AChRs differ in Inhibitors,research,lifescience,medical the two classes of cells – leading to different forms and strengths of cholinergic modulation. Predicting the functional effect of activating anatomically identified muscarinic receptors is challenging because they are coupled to G-proteins and thus to complex and diverse intracellular signaling cascades. Excitatory neurons are a well-known target for cholinergic modulation acting through the m1 AChR. Acetylcholine binding to this receptor can transiently close the m-type potassium current (Km) leading to a decrease in spike frequency adaptation and an increase in bursting (Brown et al. 1997; Yue and Yaari 2004) which probably done changes these cells’ participation in local Carfilzomib oscillatory dynamics (Fuhrmann et al. 2002). This current is likely a major contributor to cholinergic effects on m1 AChR-expressing excitatory neurons. Many PV neurons, however, (specifically those that comprise the population of fast-spiking inhibitory neurons) do not express an m-current. These are neurons that fire at high rates without significant adaptation. Thus the principal target for m1 AChR-mediated effects on these neurons is less obvious.