Descending pathways mediate adaptive optimized coding of natural stimuli in weakly electric fish

Biological systems must be flexible to environmental changes to survive. This is exemplified by the fact that sensory systems continuously adapt to changes in the environment to optimize coding and behavioral responses. However, the nature of the underlying mechanisms remains poorly understood in general. Here, we investigated the mechanisms mediating adaptive optimized coding of naturalistic stimuli with varying statistics depending on the animal’s velocity during movement. We found that central neurons adapted their responses to stimuli with different power spectral densities such as to optimally encode them, thereby ensuring that behavioral responses are, in turn, better matched to the new stimulus statistics. Sensory adaptation further required descending inputs from the forebrain as well as the raphe nuclei. Our findings thus reveal a previously unknown functional role for descending pathways in mediating adaptive optimized coding of natural stimuli that is likely generally applicable across sensory systems and species

Descending pathways generate perception of and neural responses to weak sensory input

Natural sensory stimuli frequently consist of a fast time-varying waveform whose amplitude or contrast varies more slowly. While changes in contrast carry behaviorally relevant information necessary for sensory perception, their processing by the brain remains poorly understood to this day. Here, we investigated the mechanisms that enable neural responses to and perception of low-contrast stimuli in the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We found that fish reliably detected such stimuli via robust behavioral responses. Recordings from peripheral electrosensory neurons revealed stimulus-induced changes in firing activity (i.e., phase locking) but not in their overall firing rate. However, central electrosensory neurons receiving input from the periphery responded robustly via both phase locking and increases in firing rate. Pharmacological inactivation of feedback input onto central electrosensory neurons eliminated increases in firing rate but did not affect phase locking for central electrosensory neurons in response to low-contrast stimuli. As feedback inactivation eliminated behavioral responses to these stimuli as well, our results show that it is changes in central electrosensory neuron firing rate that are relevant for behavior, rather than phase locking. Finally, recordings from neurons projecting directly via feedback to central electrosensory neurons revealed that they provide the necessary input to cause increases in firing rate. Our results thus provide the first experimental evidence that feedback generates both neural and behavioral responses to low-contrast stimuli that are commonly found in the natural environment

Feedback optimizes neural coding and perception of natural stimuli

Growing evidence suggests that sensory neurons achieve optimal encoding by matching their tuning properties to the natural stimulus statistics. However, the underlying mechanisms remain unclear. Here we demonstrate that feedback pathways from higher brain areas mediate optimized encoding of naturalistic stimuli via temporal whitening in the weakly electric fish Apteronotus leptorhynchus. While one source of direct feedback uniformly enhances neural responses, a separate source of indirect feedback selectively attenuates responses to low frequencies, thus creating a high-pass neural tuning curve that opposes the decaying spectral power of natural stimuli. Additionally, we recorded from two populations of higher brain neurons responsible for the direct and indirect descending inputs. While one population displayed broadband tuning, the other displayed high-pass tuning and thus performed temporal whitening. Hence, our results demonstrate a novel function for descending input in optimizing neural responses to sensory input through temporal whitening that is likely to be conserved across systems and species

Sprouty2 expression controls endothelial monolayer integrity and quiescence

Vascular integrity is fundamental to the formation of mature blood vessels and depends on a functional, quiescent endothelial monolayer. However, how endothelial cells enter and maintain quiescence in the presence of angiogenic factors is still poorly understood. Here we identify the fibroblast growth factor (FGF) antagonist Sprouty2 (Spry2) as a key player in mediating endothelial quiescence and barrier integrity in mouse aortic endothelial cells (MAECs): Spry2 knockout MAECs show spindle-like shapes and are incapable of forming a functional, impermeable endothelial monolayer in the presence of FGF2. Whereas dense wild type cells exhibit contact inhibition and stop to proliferate, Spry2 knockout MAECs remain responsive to FGF2 and continue to proliferate even at high cell densities. Importantly, the anti-proliferative effect of Spry2 is absent in sparsely plated cells. This cell density-dependent Spry2 function correlates with highly increased Spry2 expression in confluent wild type MAECs. Spry2 protein expression is barely detectable in single cells but steadily increases in cells growing to high cell densities, with hypoxia being one contributing factor. At confluence, Spry2 expression correlates with intact cell-cell contacts, whereas disruption of cell-cell contacts by EGTA, TNFα and thrombin decreases Spry2 protein expression. In confluent cells, high Spry2 levels correlate with decreased extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. In contrast, dense Spry2 knockout MAECs exhibit enhanced signaling by Erk1/2. Moreover, inhibiting Erk1/2 activity in Spry2 knockout cells restores wild type cobblestone monolayer morphology. This study thus reveals a novel Spry2 function, which mediates endothelial contact inhibition and barrier integrity