During spatial navigation, animals use self-motion to estimate positions through path integration. However, estimation errors accumulate over time and it is unclear how they are corrected. Here we report a new cell class ('cue cell') encoding visual cues that could be used to correct errors in path integration in mouse medial entorhinal cortex (MEC). During virtual navigation, individual cue cells exhibited firing fields only near visual cues and their population response formed sequences repeated at each cue. These cells consistently responded to cues across multiple environments. On a track with cues on left and right sides, most cue cells responded to cues only one side. During navigation in a real arena, they showed spatially stable activity and accounted for 32% of unidentified, spatially stable MEC cells. These cue cell properties demonstrate that the MEC contains a code representing spatial landmarks, which could be important for error correction during path integration.
All data generated or analyzed during this study are included in the manuscript and supporting files.
- David W Tank
- David W Tank
- Amina A Kinkhabwala
The funders had no role in the experiments or analysis in this publication.
Animal experimentation: All procedures were approved by the Princeton University Institutional Animal Care and Use Committee (IACUC protocol# 1910-15) and were in compliance with the Guide for the Care and Use of Laboratory Animals.
- Sachin Deshmukh, Indian Institute of Science Bangalore, India
© 2020, Kinkhabwala et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Axon degeneration contributes to the disruption of neuronal circuit function in diseased and injured nervous systems. Severed axons degenerate following the activation of an evolutionarily conserved signaling pathway, which culminates in the activation of SARM1 in mammals to execute the pathological depletion of the metabolite NAD+. SARM1 NADase activity is activated by the NAD+ precursor nicotinamide mononucleotide (NMN). In mammals, keeping NMN levels low potently preserves axons after injury. However, it remains unclear whether NMN is also a key mediator of axon degeneration and dSarm activation in flies. Here, we demonstrate that lowering NMN levels in Drosophila through the expression of a newly generated prokaryotic NMN-Deamidase (NMN-D) preserves severed axons for months and keeps them circuit-integrated for weeks. NMN-D alters the NAD+ metabolic flux by lowering NMN, while NAD+ remains unchanged in vivo. Increased NMN synthesis, by the expression of mouse nicotinamide phosphoribosyltransferase (mNAMPT), leads to faster axon degeneration after injury. We also show that NMN-induced activation of dSarm mediates axon degeneration in vivo. Finally, NMN-D delays neurodegeneration caused by loss of the sole NMN-consuming and NAD+-synthesizing enzyme dNmnat. Our results reveal a critical role for NMN in neurodegeneration in the fly, which extends beyond axonal injury. The potent neuroprotection by reducing NMN levels is similar to the interference with other essential mediators of axon degeneration in Drosophila.
Connections from the basolateral amygdala (BLA) to medial prefrontal cortex (PFC) regulate memory and emotion and become disrupted in neuropsychiatric disorders. The diverse roles attributed to interactions between the BLA and PFC may reflect multiple circuits nested within a wider network. To examine these circuits, we first used retrograde and anterograde anatomy to show that the rostral BLA (rBLA) and caudal BLA (cBLA) differentially project to prelimbic (PL) and infralimbic (IL) subregions of the mouse PFC. Using ex vivo whole-cell recordings and optogenetics, we then assessed which neuronal subtypes are targeted, showing that rBLA preferentially drives layer 2 (L2) cortico-amygdalar (CA) neurons in PL, whereas cBLA drives layer 5 (L5) pyramidal tract (PT) neurons in IL. We next combined in vivo silicon probe recordings and optogenetics to confirm that cBLA mainly influences IL L5, whereas rBLA primarily activates PL L2, but also evokes polysynaptic activity in PL L5. Lastly, we used soma-tagged optogenetics to explore the local circuits linking superficial and deep layers of PL, showing how rBLA can engage L2 CA neurons to impact L5 PT neuron activity. Together, our findings delineate how subregions of the BLA target distinct networks within the PFC and differentially influence output from PL and IL.