Membrane-associated periodic skeleton is a signaling platform for RTK transactivation in neurons

August 30, 2019

Zhou R, Han B, Xia C, Zhuang X

Actin, spectrin, and related molecules form a membrane-associated periodic skeleton (MPS) in neurons. The function of the MPS, however, remains poorly understood. Using super-resolution imaging, we observed that G protein-coupled receptors (GPCRs), cell adhesion molecules (CAMs), receptor tyrosine kinases (RTKs), and related signaling molecules were recruited to the MPS in response to extracellular stimuli, resulting in colocalization of these molecules and RTK transactivation by GPCRs and CAMs, giving rise to extracellular signal-regulated kinase (ERK) signaling. Disruption of the MPS prevented such molecular colocalizations and downstream ERK signaling. ERK signaling in turn caused calpain-dependent MPS degradation, providing a negative feedback that modulates signaling strength. These results reveal an important functional role of the MPS and establish it as a dynamically regulated platform for GPCR- and CAM-mediated RTK signaling.


The striatum specifies the statistics of behavior

August 29, 2019

Markowitz JE, Datta SR

Taken together, new recording technologies and automated methods for annotating behavior allowed our group, and others, to show that individual SPNs contain a relational map of action, dSPNs and iSPNs encode action complementarily, and SPNs control how movements are organized sequentially over time. This work reveals a more general role for both dSPNs and iSPNs in the process of selecting which action to perform among dozens of possible actions on a moment-by-moment basis. Thus, clinically, pathologies of the BG may be manifest both in the form and kinematics of movements and in the statistics of how movements are deployed over time.

Constructing autobiographical events within a spatial or temporal context: a comparison of two targeted episodic induction techniques

August 27, 2019

Sheldon S, Gurguryan L, Madore KP, Schacter DL.

Recalling and imagining autobiographical experiences involves constructing event representations within spatiotemporal contexts. We tested whether generating autobiographical events within a primarily spatial (where the event occurred) or temporal (the sequence of actions that occurred) context affected how the associated mental representation was constructed. We leveraged the well-validated episodic specificity induction (ESI) technique, known to influence the use of episodic processes on subsequent tasks, to develop variants that selectively enhance spatial or temporal processing. We tested the effects of these inductions on the details used to describe past and future autobiographical events. We first replicated the standard ESI effect, showing that ESI enhances generating episodic details, particularly those that are perception-based, when describing autobiographical events (Experiment 1). We then directly compared the effects of the spatial and temporal inductions (Experiment 2 and 3). When describing autobiographical events, spatial induction enhanced generating episodic details, specifically perception-based details, compared to the control or temporal inductions. A greater proportion of the episodic details generated after the temporal induction were gist-based than after the spatial induction, but this proportion did not differ from a control induction. Thus, using a spatial or temporal framework for autobiographical event generation alters the associated details that are accessed.


Idiosyncratic neural coding and neuromodulation of olfactory individuality in Drosophila

August 27, 2019

Honegger KS, Smith MA, Churgin MA, Turner GC, de Bivort BL

Innate behavioral biases and preferences can vary significantly among individuals of the same genotype. Though individuality is a fundamental property of behavior, it is not currently understood how individual differences in brain structure and physiology produce idiosyncratic behaviors. Here we present evidence for idiosyncrasy in olfactory behavior and neural responses in Drosophila We show that individual female Drosophila from a highly inbred laboratory strain exhibit idiosyncratic odor preferences that persist for days. We used in vivo calcium imaging of neural responses to compare projection neuron (second-order neurons that convey odor information from the sensory periphery to the central brain) responses to the same odors across animals. We found that, while odor responses appear grossly stereotyped, upon closer inspection, many individual differences are apparent across antennal lobe (AL) glomeruli (compact microcircuits corresponding to different odor channels). Moreover, we show that neuromodulation, environmental stress in the form of altered nutrition, and activity of certain AL local interneurons affect the magnitude of interfly behavioral variability. Taken together, this work demonstrates that individual Drosophila exhibit idiosyncratic olfactory preferences and idiosyncratic neural responses to odors, and that behavioral idiosyncrasies are subject to neuromodulation and regulation by neurons in the AL.

Origins of the concepts cause, cost, and goal in prereaching infants.

August 20, 2019

Liu S, Brooks NB, Spelke ES

We investigated the origins and interrelations of causal knowledge and knowledge of agency in 3-month-old infants, who cannot yet effect changes in the world by reaching for, grasping, and picking up objects. Across 5 experiments, n = 152 prereaching infants viewed object-directed reaches that varied in efficiency (following the shortest physically possible path vs. a longer path), goal (lifting an object vs. causing a change in its state), and causal structure (action on contact vs. action at a distance and after a delay). Prereaching infants showed no strong looking preference between a person's efficient and inefficient reaches when the person grasped and displaced an object. When the person reached for and caused a change in the state of the object on contact, however, infants looked longer when this action was inefficient than when it was efficient. Three-month-old infants also showed a key signature of adults' and older infants' causal inferences: This looking preference was abolished if a short spatial and temporal gap separated the action from its effect. The basic intuition that people are causal agents, who navigate around physical constraints to change the state of the world, may be one important foundation for infants' ability to plan their own actions and learn from the acts of others.