Extracellular recording of direct synaptic signals with a CMOS-nanoelectrode array

August 5, 2020

The synaptic connections between neurons are traditionally determined by correlating the action potentials (APs) of a pre-synaptic neuron and small-amplitude subthreshold potentials of a post-synaptic neuron using invasive intracellular techniques, such as patch clamping. Extracellular recording by a microelectrode array can non-invasively monitor network activities of a large number of neurons, but its reduced sensitivity usually prevents direct measurements of synaptic signals. Here, we demonstrate that a newly developed complementary metal-oxide-semiconductor (CMOS) nanoelectrode array (CNEA) is capable of extracellularly determining direct synaptic connections in dense, multi-layer cultures of dissociated rat neurons. We spatiotemporally correlate action potential signals of hundreds of active neurons, detect small (∼1 pA after averaging) extracellular synaptic signals at the region where pre-synaptic axons and post-synaptic dendrites/somas overlap, and use those signals to map synaptic connections. We use controlled stimulation to assess stimulation-dependent synaptic strengths and to titrate a synaptic blocker (CNQX: IC50 ∼ 1 μM). The new capabilities demonstrated here significantly enhance the utilities of CNEAs in connectome mapping and drug screening applications.

Multiplexed Optical Sensors in Arrayed Islands of Cells for multimodal recordings of cellular physiology

August 4, 2020

Cells typically respond to chemical or physical perturbations via complex signaling cascades which can simultaneously affect multiple physiological parameters, such as membrane voltage, calcium, pH, and redox potential. Protein-based fluorescent sensors can report many of these parameters, but spectral overlap prevents more than ~4 modalities from being recorded in parallel. Here we introduce the technique, MOSAIC, Multiplexed Optical Sensors in Arrayed Islands of Cells, where patterning of fluorescent sensor-encoding lentiviral vectors with a microarray printer enables parallel recording of multiple modalities. We demonstrate simultaneous recordings from 20 sensors in parallel in human embryonic kidney (HEK293) cells and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and we describe responses to metabolic and pharmacological perturbations. Together, these results show that MOSAIC can provide rich multi-modal data on complex physiological responses in multiple cell types.

Rationally inattentive intertemporal choice

July 31, 2020

Discounting of future rewards is traditionally interpreted as evidence for an intrinsic preference in favor of sooner rewards. However, temporal discounting can also arise from internal uncertainty in value representations of future events, if one assumes that noisy mental simulations of the future are rationally combined with prior beliefs. Here, we further develop this idea by considering how simulation noise may be adaptively modulated by task demands, based on principles of rational inattention. We show how the optimal allocation of mental effort can give rise to the magnitude effect in intertemporal choice. In a re-analysis of two prior data sets, and in another experiment, we reveal several behavioral signatures of this theoretical account, tying choice stochasticity to the magnitude effect. We conclude that some aspects of temporal discounting may result from a cognitively plausible adaptive response to the costs of information processing.

A Neural Network for Wind-Guided Compass Navigation

July 14, 2020

Spatial maps in the brain are most accurate when they are linked to external sensory cues. Here, we show that the compass in the Drosophila brain is linked to the direction of the wind. Shifting the wind rightward rotates the compass as if the fly were turning leftward, and vice versa. We describe the mechanisms of several computations that integrate wind information into the compass. First, an intensity-invariant representation of wind direction is computed by comparing left-right mechanosensory signals. Then, signals are reformatted to reduce the coding biases inherent in peripheral mechanics, and wind cues are brought into the same circular coordinate system that represents visual cues and self-motion signals. Because the compass incorporates both mechanosensory and visual cues, it should enable navigation under conditions where no single cue is consistently reliable. These results show how local sensory signals can be transformed into a global, multimodal, abstract representation of space.

Origin of perseveration in the trade-off between reward and complexity

July 14, 2020

When humans and other animals make repeated choices, they tend to repeat previously chosen actions independently of their reward history. This paper locates the origin of perseveration in a trade-off between two computational goals: maximizing rewards and minimizing the complexity of the action policy. We develop an information-theoretic formalization of policy complexity and show how optimizing the trade-off leads to perseveration. Analysis of two data sets reveals that people attain close to optimal trade-offs. Parameter estimation and model comparison supports the claim that perseveration quantitatively agrees with the theoretically predicted functional form (a softmax function with a frequency-dependent action bias).