Dendritic calcium signals in rhesus macaque motor cortex drive an optical brain-computer interface, bioRxiv, 2019-09-25
AbstractCalcium imaging has rapidly developed into a powerful tool for recording from large populations of neurons in vivo. Imaging in rhesus macaque motor cortex can enable the discovery of new principles of motor cortical function and can inform the design of next generation brain-computer interfaces (BCIs). Surface two-photon (2P) imaging, however, cannot presently access somatic calcium signals of neurons from all layers of macaque motor cortex due to photon scattering. Here, we demonstrate an implant and imaging system capable of chronic, motion-stabilized two-photon (2P) imaging of calcium signals from in macaques engaged in a motor task. By imaging apical dendrites, some of which originated from deep layer 5 neurons, as as well as superficial cell bodies, we achieved optical access to large populations of deep and superficial cortical neurons across dorsal premotor (PMd) and gyral primary motor (M1) cortices. Dendritic signals from individual neurons displayed tuning for different directions of arm movement, which was stable across many weeks. Combining several technical advances, we developed an optical BCI (oBCI) driven by these dendritic signals and successfully decoded movement direction online. By fusing 2P functional imaging with CLARITY volumetric imaging, we verify that an imaged dendrite, which contributed to oBCI decoding, originated from a putative Betz cell in motor cortical layer 5. This approach establishes new opportunities for studying motor control and designing BCIs.
biorxiv neuroscience 0-100-users 2019Hue tuning curves in V4 change with visual context, bioRxiv, 2019-09-25
AbstractTo understand activity in the visual cortex, researchers typically investigate how parametric changes in stimuli affect neural activity. A fundamental tenet of this approach is that the response properties of neurons in one context, e.g. color stimuli, are representative of responses in other contexts, e.g. natural scenes. This assumption is not often tested. Here, for neurons in macaque area V4, we first estimated tuning curves for hue by presenting artificial stimuli of varying hue, and then tested whether these would correlate with hue tuning curves estimated from responses to natural images. We found that neurons’ hue tuning on artificial stimuli was not representative of their hue tuning on natural images, even if the neurons were strongly color-responsive. One explanation of this result is that neurons in V4 respond to interactions between hue and other visual features. This finding exemplifies how tuning curves estimated by varying a small number of stimulus features can communicate a small and potentially unrepresentative slice of the neural response function.
biorxiv neuroscience 0-100-users 2019Multiple testing correction over contrasts for brain imaging, bioRxiv, 2019-09-20
AbstractThe multiple testing problem arises not only when there are many voxels or vertices in an image representation of the brain, but also when multiple contrasts of parameter estimates (that is, hypotheses) are tested in the same general linear model. Here we argue that a correction for this multiplicity must be performed to avoid excess of false positives. Various methods have been proposed in the literature, but few have been applied to brain imaging. Here we discuss and compare different methods to make such correction in different scenarios, showing that one classical and well known method is invalid, and argue that permutation is the best option to perform such correction due to its exactness and flexibility to handle a variety of common imaging situations.
biorxiv neuroscience 100-200-users 2019Precision calcium imaging of dense neural populations via a cell body-targeted calcium indicator, bioRxiv, 2019-09-18
AbstractMethods for one-photon fluorescent imaging of calcium dynamics in vivo are popular due to their ability to simultaneously capture the dynamics of hundreds of neurons across large fields of view, at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk between cell bodies and the surrounding neuropil, resulting in decreased signal-to-noise and artifactual correlations of neural activity. Here, we address this problem by engineering cell body-targeted variants of the fluorescent calcium indicator GCaMP6f. We screened fusions of GCaMP6f to both natural as well as engineered peptides, and identified fusions that localized GCaMP6f to within approximately 50 microns of the cell body of neurons in live mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP6f in dense neural circuits reported fewer artifactual spikes from neuropil, increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators increases neuronal signal fidelity and may facilitate even greater usage of simple, powerful, one-photon methods of population imaging of neural calcium dynamics.
biorxiv neuroscience 0-100-users 2019The Tolman-Eichenbaum Machine Unifying space and relational memory through generalisation in the hippocampal formation, bioRxiv, 2019-09-17
The hippocampal-entorhinal system is important for spatial and relational memory tasks. We formally link these domains; provide a mechanistic understanding of the hippocampal role in generalisation; and offer unifying principles underlying many entorhinal and hippocampal cell-types. We propose medial entorhinal cells form a basis describing structural knowledge, and hippocampal cells link this basis with sensory representations. Adopting these principles, we introduce the Tolman-Eichenbaum machine (TEM). After learning, TEM entorhinal cells include grid, band, border and object-vector cells. Hippocampal cells include place and landmark cells, remapping between environments. Crucially, TEM also predicts empirically recorded representations in complex non-spatial tasks. TEM predicts hippocampal remapping is not random as previously believed. Rather structural knowledge is preserved across environments. We confirm this in simultaneously recorded place and grid cells.One Sentence SummarySimple principles of representation and generalisation unify spatial and non-spatial accounts of hippocampus and explain many cell representations.
biorxiv neuroscience 100-200-users 2019Dynamic arousal signals construct memories of time and events, bioRxiv, 2019-09-11
AbstractEveryday life unfolds continuously, yet we tend to remember past experiences as discrete event sequences or episodes. Although this phenomenon has been well documented, the brain mechanisms that support the transformation of continuous experience into memorable episodes remain unknown. Here we show that a sudden change in context, or ‘event boundary’, elicits a burst of autonomic arousal, as indexed by pupil dilation. These boundaries during dynamic experience also led to the segmentation of adjacent episodes in later memory, evidenced by changes in memory for the timing, order, and perceptual details of recent event sequences. Critically, we find that distinct cognitive components of this pupil response were associated with both subjective (temporal distance judgements) and objective (temporal order discrimination) measures of episodic memory, suggesting that multiple arousal-mediated cognitive processes help construct meaningful mnemonic events. Together, these findings reveal that arousal processes may play a fundamental role in everyday memory organization.
biorxiv neuroscience 0-100-users 2019