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Born, R. T.

Publications and source records attributed to Born, R. T..

5 recordsLinked to original sources

The kinetochore proteins Ndc80 and Dsn1 are required for survival of postmitotic neurons

Dsn1 and Ndc80 are essential proteins of the kinetochore complex and required for chromosome segregation in dividing cells and for regulating development and microtubule dynamics in postmitotic neurons. With conditional deletion of floxed alleles, we here show that Dsn1 and Ndc80 are also required for the viability of postmitotic neurons, both in cultures of hippocampal and cortical neurons and in vivo in the retina. Loss of these proteins triggers apoptosis, as indicated by caspase cleavage and an increase in nuclear DNA breakage. The pro-survival function of the kinetochore components is distinct from that which was previously demonstrated for regulation of neuronal synaptogenesis. The microtubule-binding domain of Ndc80 is required for the synaptogenic functions but Ndc80 lacking this domain can nonetheless rescue the viability of neurons from which Ndc80 has been deleted. Similarly, whereas the synaptogenic function involves regulation of microtubules in axons and dendrites, a nucleus-localized Dsn1 is sufficient to rescue the viability of neurons from which Dsn1 has been deleted. Thus, postmitotic neurons retain a nuclear requirement for components of the kinetochore in order to prevent apoptosis.

neuroscience↗

Reassessing Choice Probability: What 59 Macaque Studies Tell Us About Decision-Related Activity in Visual Cortex

Choice probability (CP) quantifies the trial-by-trial covariation between a sensory neurons response and perceptual reports. Despite extensive interest in CP as a window into how perception is linked to the activity of sensory neurons, the usefulness of CP remains debated. On one hand, reported CP magnitudes vary widely across seemingly equivalent studies, questioning its utility as a metric. On the other hand, the absence of clear patterns in CP variability has made it difficult to use it to adjudicate between competing models of visual perception. Here, we performed a meta-analysis of 150 CP estimates from 59 macaque neurophysiology studies to identify factors that systematically influence CP. We confirmed the positive relationship between CP and neuronal sensitivity both across and within individual studies. When controlled for sensitivity, we found remarkable consistency in CP across varying tasks and brain regions with two notable exceptions. First, CPs were higher in tasks involving bistable percepts, reinforcing the link between CP magnitude and subjective perception. Second, CPs were smaller in area V1, supporting prior suggestions about V1s special role in visual processing. We further found a significant effect of stimulus duration on CP, providing evidence against strictly feedforward models and favoring models with substantial feedback and recurrent processing. Finally, we offer recommendations for future studies to enhance the cross-study comparability and theoretical utility of choice signals as the field transitions to large-scale population recordings. More broadly, our findings demonstrate the benefits of meta-studies that expose patterns across many different tasks and animals - yielding insights that complement large-scale population recordings.

neuroscience↗

Brain Feature Maps Reveal Progressive Animal-Feature Representations in the Ventral Stream.

What are the fundamental units of representation in the primate visual brain? While objects have become an intuitive framework for studying neurons in many parts of cortex, it is possible that neurons follow a more expressive organizational principle, such as encoding generic features present across textures, places, and objects. In this study, we used multi-electrode arrays to record from neurons in early (V1/V2), middle (V4), and late (posterior inferotemporal cortex (PIT)) areas across the visual hierarchy, estimating the local operation of each neuron over the entire visual scene. These estimates, called "heatmaps," approximate the weight sharing operation of convolutional neural networks. We found that while populations of neurons across V1, V4, and PIT responded over the full scene, they focused on salient sub-regions within object outlines. The best captured object feature class belonged to animals, not general objects, as a trend that increased over the visual hierarchy. These results show that the monkey ventral stream is partially organized to encode local animal features over objects, even as early as primary visual cortex.

neuroscience↗

A novel behavioral paradigm using mice to study predictive postural control

Postural control circuitry performs the essential function of maintaining balance and body position in response to perturbations that are either self-generated (e.g. reaching to pick up an object) or externally delivered (e.g. being pushed by another person). Human studies have shown that anticipation of predictable postural disturbances can modulate such responses. This indicates that postural control could involve higher-level neural structures associated with predictive functions, rather than being purely reactive. However, the underlying neural circuitry remains largely unknown. To enable studies of predictive postural control circuits, we developed a novel experimental paradigm for mice. In this paradigm, modeled after human studies, a dynamic platform generated reproducible translational perturbations. While mice stood bipedally atop a perch to receive water rewards, they experienced backward translations that were either unpredictable or preceded by an auditory cue. To validate the paradigm, we investigated the effect of the auditory cue on postural responses to perturbations across multiple days in three mice. These preliminary results serve to validate a new postural control experimental paradigm, opening the door to the types of neural recordings and circuit manipulations that are currently possible in mice. Significance StatementThe ability to anticipate disturbances and adjust ones posture accordingly--known as "predictive postural control"--is crucial for preventing falls and for advancing robotics. While human balance is often assessed via floor perturbations, rodent studies typically use rotarod tests. Here, we developed a postural perturbation task for freely moving mice, modeled after those used in human studies. Using a dynamic platform, we delivered reproducible perturbations with or without preceding auditory cues and quantified how the auditory cue affects postural responses to perturbations. Our work provides validation of a new postural control experimental paradigm, which opens the door to the types of neural population recordings and circuit manipulation that are currently possible in mice.

neuroscience↗

Cortico-cortical feedback from V2 exerts a powerful influence over the visually evoked local field potential and associated spike timing in V1

The local field potential (LFP) is generally thought to be dominated by synaptic activity within a few hundred microns of the recording electrode. The sudden onset of a visual stimulus causes a large downward deflection of the LFP recorded in primary visual cortex, known as a visually evoked potential (VEP), followed by rhythmic oscillations in the gamma range (30-80 Hz) that are often in phase with action potentials of nearby neurons. By inactivating higher visual areas that send feedback projections to V1, we produced a large decrease in amplitude of the VEP, and a strong attenuation of gamma rhythms in both the LFP and multi-unit activity, despite an overall increase in neuronal spike rates. Our results argue that much of the recurrent, rhythmic activity measured in V1 is strongly gated by feed-back from higher areas, consistent with models of coincidence detection that result in burst firing by layer 5 pyramidal neurons.

neuroscience↗