Innate frequency-discrimination hyperacuity in Williams-Beuren syndrome mice.

Williams-Beuren syndrome (WBS) is a rare disorder caused by hemizygous microdeletion of ∼27 contiguous genes. Despite neurodevelopmental and cognitive deficits, individuals with WBS have spared or enhanced musical and auditory abilities, potentially offering an insight into the genetic basis of auditory perception. Here, we report that the mouse models of WBS have innately enhanced frequency-discrimination acuity and improved frequency coding in the auditory cortex (ACx). Chemogenetic rescue showed frequency-discrimination hyperacuity is caused by hyperexcitable interneurons in the ACx. Haploinsufficiency of one WBS gene, Gtf2ird1, replicated WBS phenotypes by downregulating the neuropeptide receptor VIPR1. VIPR1 is reduced in the ACx of individuals with WBS and in the cerebral organoids derived from human induced pluripotent stem cells with the WBS microdeletion. Vipr1 deletion or overexpression in ACx interneurons mimicked or reversed, respectively, the cellular and behavioral phenotypes of WBS mice. Thus, the Gtf2ird1-Vipr1 mechanism in ACx interneurons may underlie the superior auditory acuity in WBS.

Neural spiking for causal inference and learning.

When a neuron is driven beyond its threshold, it spikes. The fact that it does not communicate its continuous membrane potential is usually seen as a computational liability. Here we show that this spiking mechanism allows neurons to produce an unbiased estimate of their causal influence, and a way of approximating gradient descent-based learning. Importantly, neither activity of upstream neurons, which act as confounders, nor downstream non-linearities bias the results. We show how spiking enables neurons to solve causal estimation problems and that local plasticity can approximate gradient descent using spike discontinuity learning.

A reaction-diffusion model of cholinergic retinal waves.

Prior to receiving visual stimuli, spontaneous, correlated activity in the retina, called retinal waves, drives activity-dependent developmental programs. Early-stage waves mediated by acetylcholine (ACh) manifest as slow, spreading bursts of action potentials. They are believed to be initiated by the spontaneous firing of Starburst Amacrine Cells (SACs), whose dense, recurrent connectivity then propagates this activity laterally. Their inter-wave interval and shifting wave boundaries are the result of the slow after-hyperpolarization of the SACs creating an evolving mosaic of recruitable and refractory cells, which can and cannot participate in waves, respectively. Recent evidence suggests that cholinergic waves may be modulated by the extracellular concentration of ACh. Here, we construct a simplified, biophysically consistent, reaction-diffusion model of cholinergic retinal waves capable of recapitulating wave dynamics observed in mice retina recordings. The dense, recurrent connectivity of SACs is modeled through local, excitatory coupling occurring via the volume release and diffusion of ACh. In addition to simulation, we are thus able to use non-linear wave theory to connect wave features to underlying physiological parameters, making the model useful in determining appropriate pharmacological manipulations to experimentally produce waves of a prescribed spatiotemporal character. The model is used to determine how ACh mediated connectivity may modulate wave activity, and how parameters such as the spontaneous activation rate and sAHP refractory period contribute to critical wave size variability.

Three aspects of representation in neuroscience.

Neuroscientists often describe neural activity as a representation of something, or claim to have found evidence for a neural representation, but there is considerable ambiguity about what such claims entail. Here we develop a thorough account of what 'representation' does and should do for neuroscientists in terms of three key aspects of representation. (i) Correlation: a neural representation correlates to its represented content; (ii) causal role: the representation has a characteristic effect on behavior; and (iii) teleology: a goal or purpose served by the behavior and thus the representation. We draw broadly on literature in both neuroscience and philosophy to show how these three aspects are rooted in common approaches to understanding the brain and mind. We first describe different contexts that 'representation' has been closely linked to in neuroscience, then discuss each of the three aspects in detail.

Efficient Spike-Driven Learning With Dendritic Event-Based Processing.

A critical challenge in neuromorphic computing is to present computationally efficient algorithms of learning. When implementing gradient-based learning, error information must be routed through the network, such that each neuron knows its contribution to output, and thus how to adjust its weight. This is known as the credit assignment problem. Exactly implementing a solution like backpropagation involves weight sharing, which requires additional bandwidth and computations in a neuromorphic system. Instead, models of learning from neuroscience can provide inspiration for how to communicate error information efficiently, without weight sharing. Here we present a novel dendritic event-based processing (DEP) algorithm, using a two-compartment leaky integrate-and-fire neuron with partially segregated dendrites that effectively solves the credit assignment problem. In order to optimize the proposed algorithm, a dynamic fixed-point representation method and piecewise linear approximation approach are presented, while the synaptic events are binarized during learning. The presented optimization makes the proposed DEP algorithm very suitable for implementation in digital or mixed-signal neuromorphic hardware. The experimental results show that spiking representations can rapidly learn, achieving high performance by using the proposed DEP algorithm. We find the learning capability is affected by the degree of dendritic segregation, and the form of synaptic feedback connections. This study provides a bridge between the biological learning and neuromorphic learning, and is meaningful for the real-time applications in the field of artificial intelligence.

Reconfiguring Motor Circuits for a Joint Manual and BCI Task.

Designing brain-computer interfaces (BCIs) that can be used in conjunction with ongoing motor behavior requires an understanding of how neural activity co-opted for brain control interacts with existing neural circuits. For example, BCIs may be used to regain lost motor function after stroke. This requires that neural activity controlling unaffected limbs is dissociated from activity controlling the BCI. In this study we investigated how primary motor cortex accomplishes simultaneous BCI control and motor control in a task that explicitly required both activities to be driven from the same brain region (i.e. a dual-control task). Single-unit activity was recorded from intracortical, multi-electrode arrays while a non-human primate performed this dual-control task. Compared to activity observed during naturalistic motor control, we found that both units used to drive the BCI directly (control units) and units that did not directly control the BCI (non-control units) significantly changed their tuning to wrist torque. Using a measure of effective connectivity, we observed that control units decrease their connectivity. Through an analysis of variance we found that the intrinsic variability of the control units has a significant effect on task proficiency. When this variance is accounted for, motor cortical activity is flexible enough to perform novel BCI tasks that require active decoupling of natural associations to wrist motion. This study provides insight into the neural activity that enables a dual-control brain-computer interface.

Quantifying How Staining Methods Bias Measurements of Neuron Morphologies.

The process through which neurons are labeled is a key methodological choice in measuring neuron morphology. However, little is known about how this choice may bias measurements. To quantify this bias we compare the extracted morphology of neurons collected from the same rodent species, experimental condition, gender distribution, age distribution, brain region and putative cell type, but obtained with 19 distinct staining methods. We found strong biases on measured features of morphology. These were largest in features related to the coverage of the dendritic tree (e.g., the total dendritic tree length). Understanding measurement biases is crucial for interpreting morphological data.

Dimensionality reduction in neuroscience.

The nervous system extracts information from its environment and distributes and processes that information to inform and drive behaviour. In this task, the nervous system faces a type of data analysis problem, for, while a visual scene may be overflowing with information, reaching for the television remote before us requires extraction of only a relatively small fraction of that information. We could care about an almost infinite number of visual stimulus patterns, but we don't: we distinguish two actors' faces with ease but two different images of television static with significant difficulty. Equally, we could respond with an almost infinite number of movements, but we don't: the motions executed to pick up the remote are highly stereotyped and related to many other grasping motions. If we were to look at what was going on inside the brain during this task, we would find populations of neurons whose electrical activity was highly structured and correlated with the images on the screen and the action of localizing and picking up the remote.

Analysis of Neuronal Spike Trains, Deconstructed.

As information flows through the brain, neuronal firing progresses from encoding the world as sensed by the animal to driving the motor output of subsequent behavior. One of the more tractable goals of quantitative neuroscience is to develop predictive models that relate the sensory or motor streams with neuronal firing. Here we review and contrast analytical tools used to accomplish this task. We focus on classes of models in which the external variable is compared with one or more feature vectors to extract a low-dimensional representation, the history of spiking and other variables are potentially incorporated, and these factors are nonlinearly transformed to predict the occurrences of spikes. We illustrate these techniques in application to datasets of different degrees of complexity. In particular, we address the fitting of models in the presence of strong correlations in the external variable, as occurs in natural sensory stimuli and in movement. Spectral correlation between predicted and measured spike trains is introduced to contrast the relative success of different methods.