Robust perception of self-motion requires integration of visual motion signals with nonvisual cues. Neurons in the dorsal subdivision of the medial superior temporal area (MSTd) may be involved in this sensory integration, because they respond selectively to global patterns of optic flow, as well as translational motion in darkness. Using a virtual-reality system, we have characterized the three-dimensional (3D) tuning of MSTd neurons to heading directions defined by optic flow alone, inertial motion alone, and congruent combinations of the two cues. Among 255 MSTd neurons, 98% exhibited significant 3D heading tuning in response to optic flow, whereas 64% were selective for heading defined by inertial motion. Heading preferences for visual and inertial motion could be aligned but were just as frequently opposite. Moreover, heading selectivity in response to congruent visual/vestibular stimulation was typically weaker than that obtained using optic flow alone, and heading preferences under congruent stimulation were dominated by the visual input. Thus, MSTd neurons generally did not integrate visual and nonvisual cues to achieve better heading selectivity. A simple two-layer neural network, which received eye-centered visual inputs and head-centered vestibular inputs, reproduced the major features of the MSTd data. The network was trained to compute heading in a head-centered reference frame under all stimulus conditions, such that it performed a selective reference-frame transformation of visual, but not vestibular, signals. The similarity between network hidden units and MSTd neurons suggests that MSTd may be an early stage of sensory convergence involved in transforming optic flow information into a (head-centered) reference frame that facilitates integration with vestibular signals.

Dense connectomic mapping of neuronal circuits is limited by the time and effort required to analyze 3D electron microscopy (EM) datasets. Algorithms designed to automate image segmentation suffer from substantial error rates and require significant manual error correction. Any improvement in segmentation error rates would therefore directly reduce the time required to analyze 3D EM data. We explored preserving extracellular space (ECS) during chemical tissue fixation to improve the ability to segment neurites and to identify synaptic contacts. ECS preserved tissue is easier to segment using machine learning algorithms, leading to significantly reduced error rates. In addition, we observed that electrical synapses are readily identified in ECS preserved tissue. Finally, we determined that antibodies penetrate deep into ECS preserved tissue with only minimal permeabilization, thereby enabling correlated light microscopy (LM) and EM studies. We conclude that preservation of ECS benefits multiple aspects of the connectomic analysis of neural circuits.DOI: http://dx.doi.org/10.7554/eLife.08206.001

Some neurons in auditory cortex respond to recent stimulus history by adapting their response functions to track stimulus statistics directly, as might be expected. In contrast, some neurons respond to loud sounds by adjusting their response functions away from high intensities and consequently remain sensitive to softer sounds. In marmoset monkey auditory cortex, the latter type of adaptation appears to exist only in neurons tuned to stimulus intensity.

In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to layer 4 as well as the ear and eye opening. In developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons deep in the developing white matter. We investigated if subplate neurons respond to sensory stimuli. Using electrophysiological recordings in young ferrets, we show that auditory cortex neurons respond to sound at very young ages, even before the opening of the ears. Single unit recordings showed that auditory responses emerged first in cortical subplate neurons. Subsequently, responses appeared in the future thalamocortical input layer 4, and sound-evoked spike latencies were longer in layer 4 than in subplate, consistent with the known relay of thalamic information to layer 4 by subplate neurons. Electrode array recordings show that early auditory responses demonstrate a nascent topographic organization, suggesting that topographic maps emerge before the onset of spiking responses in layer 4. Together our results show that sound-evoked activity and topographic organization of the cortex emerge earlier and in a different layer than previously thought. Thus, early sound experience can activate and potentially sculpt subplate circuits before permanent thalamocortical circuits to layer 4 are present, and disruption of this early sensory activity could be utilized for early diagnosis of developmental disorders.