Shunt peaking in neural membranes

Capacitance limits the bandwidth of engineered and biological electrical circuits because it determines the gain–bandwidth product (GBWP). With a fixed GBWP, bandwidth can only be improved by decreasing gain. In engineered circuits, an inductance reduces this limitation through shunt peaking but no equivalent mechanism has been reported for biological circuits. We show that in blowfly photoreceptors a voltage-dependent K + conductance, the fast delayed rectifier (FDR), produces shunt peaking thereby increasing bandwidth without reducing gain. Furthermore, the FDR's time constant is close to the value that maximizes the photoreceptor GBWP while reducing distortion associated with the creation of a wide-band filter. Using a model of the honeybee drone photoreceptor, we also show that a voltage-dependent Na + conductance can produce shunt peaking. We argue that shunt peaking may be widespread in graded neurons and dendrites.

Microglial Immunoreceptor Tyrosine-Based Activation and Inhibition Motif Signaling in Neuroinflammation

Elimination of extracellular aggregates and apoptotic neural membranes without inflammation is crucial for brain tissue homeostasis. In the mammalian central nervous system, essential molecules in this process are the Fc receptors and the DAP12-associated receptors which both trigger the microglial immunoreceptor tyrosine-based activation motif- (ITAM-) Syk-signaling cascade. Microglial triggering receptor expressed on myeloid cells-2 (TREM2), signal regulatory protein-1, and complement receptor-3 (CD11b/CD18) signal via the adaptor protein DAP12 and activate phagocytic activity of microglia. Microglial ITAM-signaling receptors are counter-regulated by immunoreceptor tyrosine-based inhibition motif- (ITIM-) signaling molecules such as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs can suppress the proinflammatory and phagocytic activity of microglia via ITIM signaling. Moreover, microglial neurotoxicity is alleviated via interaction of Siglec-11 with sialic acids on the neuronal glycocalyx. Thus, ITAM- and ITIM-signaling receptors modulate microglial phagocytosis and cytokine expression during neuroinflammatory processes. Their dysfunction could lead to impaired phagocytic clearance and neurodegeneration triggered by chronic inflammation.