Nociceptors detect damaging stimuli and evoke pain in healthy animals. We conducted an optogenetic activation screen to identify genetically defined nociceptor populations that elicit place aversion and nocifensive behaviors in response to stimulation. Smr2Cre- and Bmpr1bCre-labeled Aδ high-threshold mechanoreceptors (HTMRs) emerged as two of the few nociceptor populations, and we focused on investigating their physiological, morphological, functional, and synaptic properties. These neurons densely innervate skin and other organs, are activated only by intense, potentially damaging stimuli, and are necessary for protective responses to sharp mechanical stimuli. Centrally, Aδ-HTMR projections span multiple spinal segments and terminate across spinal cord laminae, forming strong, monosynaptic connections onto anterolateral tract projection neurons, including antenna cells of the deep dorsal horn. Aδ-HTMRs also engage a local spinal reflex circuit, enabling a remarkably rapid limb withdrawal. Thus, Aδ-HTMRs are myelinated nociceptors with unique properties that can be exploited for the development of new analgesics.

Recording and manipulating brain activity during behavior is critical to understanding the underlying mechanisms of decision-making. Linking neural activity to behavior requires behavioral hardware and software tightly integrated with recording and perturbation systems on a shared clock. We built SPOUT (State-machine Platform for Operant Uni/dual-spout Tasks), an open-source, Teensy-driven state-machine platform with a MATLAB interface that runs 10 unique decision-making tasks (with dozens of variations available through user-friendly settings) to study behavior in head-restrained mice. The platform is built on several custom hardware devices: a dual-lick detector, headplate designs for optogenetics and two-photon calcium imaging, a three-axis motorized spout manipulator, and an optogenetics power modulator. The firmware differentiates between one and two lick spout tasks and can be controlled by a user-friendly interface. Task settings can be selected through the interface or by loading predefined settings files. We validated the clock speed and lick detection against an independent, external acquisition system and identified highly precise, sub-millisecond detection of single licks. Using a pseudo-random synchronization pulse generated by SPOUT, we corrected for missing data due to glitches in the acquisition system and clock drift. We showcase the versatility of SPOUT by training mice on an uninstructed lick-left/lick-right task in which the rewarded side switches unexpectedly and found that mice use history-dependent action-outcome associations to guide future behavior. Transiently inhibiting the anterior lateral motor cortex (ALM) during cue presentation induced contralateral deficits, without affecting ipsilateral trials. Finally, two-photon imaging of ALM neurons revealed stronger population responses during contralateral choice licks compared to ipsilateral ones. Together, SPOUT offers an open-source, affordable platform to study decision-making in head-restrained mice while combining neural recordings and manipulations.

SUMMARY:Fully implantable electronic devices in freely roaming animal models are useful in biomedical research, but their development is prohibitively resource intensive for many laboratories. The advent of miniaturized microcontrollers with onboard wireless data exchange capabilities has enabled cost-efficient development of myriad do-it-yourself electronic devices that are easily customizable with open-source software ( https://www.arduino.cc/ ). Likewise, the global proliferation of mobile devices has led to the development of low-cost miniaturized wireless power technology. The authors present a low-cost, rechargeable, and fully implantable electronic device comprising a commercially available, open-source, wirelessly powered microcontroller that is readily customizable with myriad readily available miniature sensors and actuators. The authors demonstrate the utility of this platform for chronic nerve stimulation in the freely roaming rat with intermittent wireless charging over 4 weeks. Device assembly was achieved within 2 hours and necessitated only basic soldering equipment. Component costs totaled $115 per device. Wireless data transfer and wireless recharging of device batteries was achieved within 30 minutes, and no harmful heat generation occurred during charging or discharging cycles, as measured by external thermography and internal device temperature monitoring. Wireless communication enabled triggered cathodic pulse stimulation of the facial nerve at various user-selected programmed frequencies (1, 5, and 10 Hz) for periods of 4 weeks or longer. This implantable electronic platform could be further miniaturized and expanded to study a vast array of biomedical research questions in live animal models.CLINICAL RELEVANCE STATEMENT:The clinical relevance of electrical stimulation in neural recovery remains controversial, and long-term neural stimulation in small animal models is challenging. We have developed a low-cost, fully implantable, wirelessly powered nerve stimulation device to facilitate further research in nerve stimulation in animal models.

Vibrations are ubiquitous in nature, shaping behavior across the animal kingdom. For mammals, mechanical vibrations acting on the body are detected by mechanoreceptors of the skin and deep tissues and processed by the somatosensory system, while sound waves traveling through air are captured by the cochlea and encoded in the auditory system. Here, we report that mechanical vibrations detected by the body’s Pacinian corpuscle neurons, which are unique in their ability to entrain to high frequency (40-1000 Hz) environmental vibrations, are prominently encoded by neurons in the lateral cortex of the inferior colliculus (LCIC) of the midbrain. Remarkably, most LCIC neurons receive convergent Pacinian and auditory input and respond more strongly to coincident tactile-auditory stimulation than to either modality alone. Moreover, the LCIC is required for behavioral responses to high frequency mechanical vibrations. Thus, environmental vibrations captured by Pacinian corpuscles are encoded in the auditory midbrain to mediate behavior.

The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hinder-ing our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Ad-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.

Suppressing sensory arousal is critical for sleep, with deeper sleep requiring stronger sensory suppression. The mechanisms that enable sleeping animals to largely ignore their surroundings are not well understood. We show that the responsiveness of sleeping flies and mice to mechanical vibrations is better suppressed when the diet is protein rich. In flies, we describe a signaling pathway through which information about ingested proteins is conveyed from the gut to the brain to help suppress arousability. Higher protein concentration in the gut leads to increased activity of enteroendocrine cells that release the peptide CCHa1. CCHa1 signals to a small group of dopamine neurons in the brain to modulate their activity; the dopaminergic activity regulates the behavioral responsiveness of animals to vibrations. The CCHa1 pathway and dietary proteins do not influence responsiveness to all sensory inputs, showing that during sleep, different information streams can be gated through independent mechanisms.

The rapid spread of COVID-19 and disruption of normal supply chains has resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information describing design and performance criteria for PAPRs represents a substantial barrier to mitigating shortages. We sought to apply open-source product development (OSPD) to PAPRs to enable alternative sources of supply and further innovation. We describe the design, prototyping, validation, and user testing of locally manufactured, modular, PAPR components, including filter cartridges and blower units, developed by the Greater Boston Pandemic Fabrication Team (PanFab). Two designs, one with a fully custom-made filter and blower unit housing, and the other with commercially available variants (the “Custom” and “Commercial” designs, respectively) were developed; the components in the Custom design are interchangeable with those in Commercial design, although the form factor differs. The engineering performance of the prototypes was measured and safety validated using National Institutes for Occupational Safety and Health (NIOSH)-equivalent tests on apparatus available under pandemic conditions at university laboratories. Feedback was obtained from four individuals; two clinicians working in ambulatory clinical care and two research technical staff for whom PAPR use is standard occupational PPE; these individuals were asked to compare PanFab prototypes to commercial PAPRs from the perspective of usability and suggest areas for improvement. Respondents rated the PanFab Custom PAPR a 4 to 5 on a 5 Likert-scale 1) as compared to current PPE options, 2) for the sense of security with use in a clinical setting, and 3) for comfort compared to standard, commercially available PAPRs. The three other versions of the designs (with a Commercial blower unit, filter, or both) performed favorably, with survey responses consisting of scores ranging from 3 to 5. Engineering testing and clinical feedback demonstrate that the PanFab designs represent favorable alternatives to traditional PAPRs in terms of user comfort, mobility, and sense of security. A nonrestrictive license promotes innovation in respiratory protection for current and future medical emergencies.

Background: Disease processes causing increased neural compartment pressure may induce transient or permanent neural dysfunction. Surgical decompression can prevent and reverse such nerve damage. Owing to insufficient evidence from controlled studies, the efficacy and optimal timing of decompression surgery remains poorly characterized for several entrapment syndromes. New method: We describe the design, manufacture, and validation of a device for study of entrapment neuropathy in a small animal model. This device applies graded extrinsic pressure to a peripheral nerve and wirelessly transmits applied pressure levels in real-time. We implanted the device in rats applying low (under 100 mmHg), intermediate (200-300 mmHg) and high (above 300 mmHg) pressures to induce entrapment neuropathy of the facial nerve to mimic Bell's palsy. Facial nerve function was quantitatively assessed by tracking whisker displacements before, during, and after compression. Results: At low pressure, no functional loss was observed. At intermediate pressure, partial functional loss developed with return of normal function several days after decompression. High pressure demonstrated complete functional loss with incomplete recovery following decompression. Histology demonstrated uninjured, Sunderland grade III, and Sunderland grade V injury in nerves exposed to low, medium, and high pressure, respectively. Comparison with existing methods: Existing animal models of entrapment neuropathy are limited by inability to measure and titrate applied pressure over time. Conclusions: Described is a miniaturized, wireless, fully implantable device for study of entrapment neuropathy in a murine model, which may be broadly employed to induce various degrees of neural dysfunction and functional recovery in live animal models.

Despite decades of investigation, the neuronal and molecular bases of motivational states remain mysterious. We have recently developed a novel, reductionist, and scalable system for in-depth investigation of motivation using the mating drive of male Drosophila melanogaster (Drosophila), the methods for which we detail here. The behavioral paradigm centers on the finding that male mating drive decreases alongside fertility over the course of repeated copulations and recovers over ~3 d. In this system, the powerful neurogenetic tools available in the fly converge with the genetic accessibility and putative wiring diagram available for sexual behavior. This convergence allows rapid isolation and interrogation of small neuronal populations with specific motivational functions. Here we detail the design and execution of the satiety assay that is used to measure and alter courtship motivation in the male fly. Using this assay, we also demonstrate that low male mating drive can be overcome by stimulating dopaminergic neurons. The satiety assay is simple, affordable, and robust to influences of genetic background. We expect the satiety assay to generate many new insights into the neurobiology of motivational states.

Magnetic levitation is a technique for measuring the density and the magnetic properties of objects suspended in a paramagnetic field. We describe a novel magnetic levitation-based method that can specifically detect cell membrane-bound and soluble antigens by measurable changes in levitation height that result from the formation of antibody-coated bead and antigen complex. We demonstrate our method's ability to sensitively detect an array of membrane-bound and soluble antigens found in blood, including T-cell antigen CD3, eosinophil antigen Siglec-8, red blood cell antigens CD35 and RhD, red blood cell-bound Epstein-Barr viral particles, and soluble IL-6, and validate the results by flow cytometry and immunofluorescence microscopy performed in parallel. Additionally, employing an inexpensive, single lens, manual focus, wifi-enabled camera, we extend the portability of our method for its potential use as a point-of-care diagnostic assay.

Despite decades of investigation, the neuronal and molecular bases of motivational states remain mysterious. We have recently developed a novel, reductionist, and scalable system for in-depth investigation of motivation using the mating drive of male Drosophila melanogaster (Drosophila), the methods for which we detail here. The behavioral paradigm centers on the finding that male mating drive decreases alongside fertility over the course of repeated copulations and recovers over ~3 d. In this system, the powerful neurogenetic tools available in the fly converge with the genetic accessibility and putative wiring diagram available for sexual behavior. This convergence allows rapid isolation and interrogation of small neuronal populations with specific motivational functions. Here we detail the design and execution of the satiety assay that is used to measure and alter courtship motivation in the male fly. Using this assay, we also demonstrate that low male mating drive can be overcome by stimulating dopaminergic neurons. The satiety assay is simple, affordable, and robust to influences of genetic background. We expect the satiety assay to generate many new insights into the neurobiology of motivational states.

Magnetic levitation has emerged as a technique that offers the ability to differentiate between cells with different densities. We have developed a magnetic levitation system for this purpose that distinguishes not only different cell types but also density differences in cells of the same type. This small-scale system suspends cells in a paramagnetic medium in a capillary placed between two rare earth magnets, and cells levitate to an equilibrium position determined solely by their density. Uniform reference beads of known density are used in conjunction with the cells as a means to quantify their levitation positions. In one implementation images of the levitating cells are acquired with a microscope, but here we also introduce a cell phone-based device that integrates the magnets, capillary, and a lens into a compact and portable unit that acquires images with the phone's camera. To demonstrate the effectiveness of magnetic levitation in cell density analysis we carried out levitation experiments using red blood cells with artificially altered densities, and also levitated those from donors. We observed that we can distinguish red blood cells of an anemic donor from those that are healthy. Since a plethora of disease states are characterized by changes in cell density magnetic cell levitation promises to be an effective tool in identifying and analyzing pathologic states. Furthermore, the low cost, portability, and ease of use of the cell phone-based system may potentially lead to its deployment in low-resource environments.

This depository contains raw data from 14 experiments performed on adult locusts. The data are contained in HDF5 files (http://www.hdfgroup.org/HDF5/). They are stored as compressed integers coded on 16 bits as they came out of the A/D card. Recording details can be found in Pouzat, Mazor and Laurent (2002) Using noise signature to optimize spike-sorting and to assess neuronal classification quality. Journal of Neuroscience Methods 122: 43-57 (a pre-print version is available: http://xtof.perso.math.cnrs.fr/pdf/Pouzat+:2002.pdf). Each data file is subdivided in Groups corresponding the type of acquisition performed: one or several epochs of spontaneous activity recording; repetitive stimulation with a given odor. Each group is made of one (if say a single epoch of 60 seconds of spontaneous recording was made) or several (if say 100 stimulation with Citral were made) (sub-)groups containing the data of all the channels that were recorded during that epoch. Each of these sub-groups is made of 4 to 16 data sets: 1 dimensional arrays containing the raw data recorded from one of the 16 channels of our probe (made of 4 tetrodes) during a single acquisition epoch. All channels were sampled at 15 kHz. Each data file has attributes (metadata) README and LabBook. The first, README contains a shortened version of the present text; the second, LabBook contains a transcript of the lab book corresponding to the experiment. Most groups have a log_file_content attribute. This attribute contains a copy a text file that was automatically generated during data acquisition. Some recording details can be found there as well as the precise time and data of each recorded epoch. The data were kept for 14 years on CDs and about a third of the recordings got lost because of CD corruption! What's left still make 15 GBytes of data after compression: a substantial amount. This CD corruption explains why some groups don't have a log_file_content attribute: it was on a corrupted CD. Of the 14 experiments, 12 contain antennal lobe (the first olfactory relay of insects) recordings, 1 contains antennal lobe and alpha lobe recordings and 1 contains only alpha lobe recordings. Here the alpha lobe location should be taken with a little bit of caution since the latter is not as easy to locate as the antennal lobe in the locust. All data files start with the locust prefix, followed by the experiment year, month and date, like locust20000214.hdf5 an experiment performed on February 14 2000. Due to file size restriction on Zenodo, two experiments are split into two data files: locust20010124b_part1.hdf5 and locust20010124b_part2.hdf5 as well as locust20010214_part1.hdf5 and locust20010214_part2.hdf5. On two dates, two different experiments were performed: locust20010124a.hdf5 and locust20010124b_part1.hdf5 / locust20010124b_part2.hdf5 as well as locust20010208a.hdf5 and locust20010208b.hdf5. When a stimulation was applied, the following code is used: Odor name / Number of stimulation / Inter-stimulation interval / duration before the odor pulse / odor pulse duration / post pulse duration [odor dilution when several dilutions were used]. All times are in seconds. A very brief description at the group level of the files content follows (see the LabBook attribute of each individual file for details): locust20000214.hdf5: Citral / 70 / 30 / 3 / 0.5 / 6.5 Cherry / 120 / 30 / 3 / 0.5 / 6.5 Octaldehyde / 60 / 30 / 3 / 0.5 / 6.5 locust20000421.hdf5: Spontaneous: 60 seconds of spontaneous activity 1-Hexanol / 30 / 10 / 3 / 1 / 5.5 Hexanal / 25 / 10 / 3 / 1 / 5.5 Cis-3-hexen-1-ol / 25 / 10 / 3 / 1 / 5.5 Trans-2-hexen-1-ol / 25 / 10 / 3 / 1 / 5.5 1-Hexen-3-ol / 25 / 10 / 3 / 1 / 5.5 3-Pentanone / 25 / 10 / 3 / 1 / 5.5 1-Heptanol / 25 / 10 / 3 / 1 / 5.5 1-Octanol / 25 / 10 / 3 / 1 / 5.5 2-Heptanone / 25 / 10 / 3 / 1 / 5.5 3-Heptanone / 25 / 10 / 3 / 1 / 5.5 Citral / 25 / 10 / 3 / 1 / 5.5 Apple / 25 / 10 / 3 / 1 / 5.5 Mint / 25 / 10 / 3 / 1 / 5.5 Strawberry / 25 / 10 / 3 / 1 / 5.5 Octaldehyde / 25 / 10 / 3 / 1 / 5.5 1-Octanol / 25 / 10 / 3 / 1 / 5.5 [10^-5] 1-Octanol / 25 / 10 / 3 / 1 / 5.5 [10^-4] 1-Octanol / 25 / 10 / 3 / 1 / 5.5 [10^-3] 1-Octanol / 25 / 10 / 3 / 1 / 5.5 [10^-2] 1-Octanol / 25 / 10 / 3 / 1 / 5.5 [10^-1] 1-Octanol / 25 / 10 / 3 / 1 / 5.5 [1] locust20000423.hdf5: Spontaneous first: 60 seconds of spontaneous activity 1-Hexanol / 25 / 10 / 3 / 1 / 5.5 Hexanal / 25 / 10 / 3 / 1 / 5.5 Cis-3-hexen-1-ol / 25 / 10 / 3 / 1 / 5.5 1-Hexen-3-ol / 25 / 10 / 3 / 1 / 5.5 1-Heptanol / 25 / 10 / 3 / 1 / 5.5 2-Heptanone / 25 / 10 / 3 / 1 / 5.5 3-Heptanone / 25 / 10 / 3 / 1 / 5.5 Citral / 25 / 10 / 3 / 1 / 5.5 Apple / 25 / 10 / 3 / 1 / 5.5 Amyl Acetate / 25 / 10 / 3 / 1 / 5.5 1-Hexanol / 25 / 10 / 3 / 1 / 5.5 Spontaneous second: 60 seconds of spontaneous activity locust20000613.hdf5: Cis-3-hexen-1-ol / 50 / 30 / 3 / 1 / 16 [1] Cis-3-hexen-1-ol / 10 / 30 / 3 / 1 / 16 [1/100] Cis-3-hexen-1-ol / 50 / 30 / 3 / 1 / 16 [1/10] Cis-3-hexen-1-ol / 50 / 30 / 3 / 1 / 16 [1] Cherry / 21 / 30 / 3 / 1 / 16 locust20000616.hdf5: Spontaneous first: 60 seconds of spontaneous activity Cis-3-hexen-1-ol / 50 / 30 / 3 / 1 / 16 [1] Spontaneous second: 60 seconds of spontaneous activity Spontaneous third: 60 seconds of spontaneous activity Cis-3-hexen-1-ol / 50 / 30 / 3 / 1 / 16 [1/100] Cis-3-hexen-1-ol / 50 / 30 / 3 / 1 / 16 [1/10] locust20000901.hdf5: Vanilla / 5 / 30 / 3 / 1 / 16 Spontaneous: 60 seconds of spontaneous activity Cherry / 30 / 30 / 3 / 1 / 16 Spontaneous: 60 seconds of spontaneous activity Benzaldehyde / 30 / 30 / 3 / 1 / 16 Spontaneous: 60 seconds of spontaneous activity Mint / 20 / 30 / 3 / 1 / 16 Hexanal / 15 / 30 / 3 / 1 / 16 Spontaneous: 60 seconds of spontaneous activity Cis-3-hexen-1-ol / 30 / 30 / 3 / 1 / 16 Spontaneous: 60 seconds of spontaneous activity Trans-2-hexen-1-ol / 30 / 30 / 3 / 1 / 16 locust20010124a.hdf5: Spontaneous: 2x29 seconds of spontaneous activity Spontaneous: 60x29 seconds of spontaneous activity Spontaneous: 80x29 seconds of spontaneous activity locust20010124b_part1.hdf5 and locust20010124b_part2.hdf5: Spontaneous: 60x29 seconds of spontaneous activity Spontaneous: 191x29 seconds of spontaneous activity Spontaneous: 59x29 seconds of spontaneous activity locust20010131.hdf5: Spontaneous: 90x29 seconds of spontaneous activity Spontaneous: 70x29 seconds of spontaneous activity Spontaneous: 5x59 seconds of spontaneous activity Spontaneous: 3x59 seconds of spontaneous activity Spontaneous: 3x59 seconds of spontaneous activity Spontaneous: 3x59 seconds of spontaneous activity Spontaneous: 3x59 seconds of spontaneous activity Spontaneous: 3x59 seconds of spontaneous activity Spontaneous: 3x59 seconds of spontaneous activity WithoutAntenna: 3x59 seconds of spontaneous activity (after antennal nerve cut) WithoutAntenna: 3x59 seconds of spontaneous activity (after antennal nerve cut) WithoutAntenna: 3x59 seconds of spontaneous activity (after antennal nerve cut) locust20010201: Continuous: 90x29 seconds of spontaneous activity Continuous: 20x29 seconds of spontaneous activity Citral / 50 / 30 / 3 / 1 / 25 Citral / 50 / 30 / 10 / 1 / 18 Citral / 50 / 30 / 10 / 1 / 18 Continuous: 50x29 seconds of spontaneous activity Continuous: 45x29 seconds of spontaneous activity locust20010208a.hdf5: Spontaneous: 50x29 seconds of spontaneous activity Spontaneous: 80x29 seconds of spontaneous activity locust20010208b.hdf5: Spontaneous: 50x29 seconds of spontaneous activity Spontaneous: 50x29 seconds of spontaneous activity Citral / 50 / 30 / 10 / 1 / 18 Citral / 120 / 30 / 10 / 1 / 18 Citral / 50 / 30 / 10 / 1 / 18 Citral / 25 / 30 / 10 / 1 / 18 locust20010214_part1.hdf5 and locust20010214_part2.hdf5: Spontaneous: 30x29 seconds of spontaneous activity Spontaneous: 30x29 seconds of spontaneous activity Cis-3-hexen-1-ol / 25 / 30 / 10 / 1 / 18 Citral / 25 / 30 / 10 / 1 / 18 Vanilla / 25 / 30 / 10 / 1 / 18 Octanol / 25 / 30 / 10 / 1 / 18 Mint / 25 / 30 / 10 / 1 / 18 Cis-3-hexen-1-ol / 25 / 30 / 10 / 1 / 18 Spontaneous: 30x29 seconds of spontaneous activity Spontaneous: 30x29 seconds of spontaneous activity Cis-3-hexen-1-ol / 30 / 30 / 10 / 1 / 18 Cis-3-hexen-1-ol / 11 / 30 / 10 / 1 / 18 Cis-3-hexen-1-ol / 30 / 30 / 10 / 1 / 18 Cis-3-hexen-1-ol / 30 / 30 / 10 / 1 / 18 locust20010217.hdf5: Spontaneous: 10x29 seconds of spontaneous activity Spontaneous: 2x29 seconds of spontaneous activity Spontaneous: 30x29 seconds of spontaneous activity Spontaneous: 10x29 seconds of spontaneous activity Spontaneous: 10x29 seconds of spontaneous activity Spontaneous: 10x29 seconds of spontaneous activity Spontaneous: 10x29 seconds of spontaneous activity Spontaneous: 10x29 seconds of spontaneous activity Spontaneous: 10x29 seconds of spontaneous activity

Raw data from a tetrode recording from the antennal lobe (the first olfactory relay) of a locust, Schistocerca americana. The data were filtered (before A/D conversion) between 300 and 5000 Hz and sampled at 15 kHz. See Pouzat, Mazor and Laurent (2002) Journal of Neuroscience Methods 122(1): 43--57 for recording details. The data were recorded with a "Michigan probe", now sold by NeuroNexus (http://neuronexus.com/). A picture of the probe--made of 16 channels making 4 tetrodes--can be seen on slide 3 of DOI:10.5281/zenodo.14660. Good data were visible only on one of the tetrodes made of channel 9 / 11 / 13 / 16 and only data from these channels were recorded. The "LabBook" attribute contains transcript of the actual lab book with details about the acquisition. In short: 1 hour and 40 minutes of spontaneous activity was recorded as well as responses to 150 stimulation with citral. Each data set has a "log_file_content" attribute containing a copy of actual log file automatically generated during the acquisition. The stimulation protocol as well as the precise times of beginning and end of trial acquisition can be found there. The data are in HDF5 format (http://www.hdfgroup.org/HDF5/). Recordings performed by Christophe Pouzat and Ofer Mazor in the laboratory of Gilles Laurent (California Institute of Technology) in February 2001.

In Drosophila, just as in vertebrates, changes in external temperature are encoded by bidirectional opponent thermoreceptor cells: some cells are excited by warming and inhibited by cooling, whereas others are excited by cooling and inhibited by warming. The central circuits that process these signals are not understood. In Drosophila, a specific brain region receives input from thermoreceptor cells. Here we show that distinct genetically identified projection neurons (PNs) in this brain region are excited by cooling, warming, or both. The PNs excited by cooling receive mainly feed-forward excitation from cool thermoreceptors. In contrast, the PNs excited by warming ('warm-PNs') receive both excitation from warm thermoreceptors and crossover inhibition from cool thermoreceptors through inhibitory interneurons. Notably, this crossover inhibition elicits warming-evoked excitation, because warming suppresses tonic activity in cool thermoreceptors. This in turn disinhibits warm-PNs and sums with feed-forward excitation evoked by warming. Crossover inhibition could cancel non-thermal activity (noise) that is positively correlated among warm and cool thermoreceptor cells, while reinforcing thermal activity which is anti-correlated. Our results show how central circuits can combine signals from bidirectional opponent neurons to construct sensitive and robust neural codes.

Projection neurons (PNs) in the locust antennal lobe exhibit odor-specific dynamic responses. We studied a PN population, stimulated with five odorants and pulse durations between 0.3 and 10 s. Odor representations were characterized as time series of vectors of PN activity, constructed from the firing rates of all PNs in successive 50 ms time bins. Odor representations by the PN population can be described as trajectories in PN state space with three main phases: an on transient, lasting 1-2 s; a fixed point, stable for at least 8 s; and an off transient, lasting a few seconds as activity returns to baseline. Whereas all three phases are odor specific, optimal stimulus separation occurred during the transients rather than the fixed points. In addition, the PNs' own target neurons respond least when their PN-population input stabilized at a fixed point. Steady-state measures of activity thus seem inappropriate to understand the neural code in this system.

Sensory information is represented in the brain through the activity of populations of neurons. How this information is encoded and how it is processed and read out are crucial questions in neuroscience. The work presented here examines these issues using an insect brain model system. Specifically, this work addresses how odor information is represented across a population of neurons in this relatively simple nervous system. It asks how the dynamics of a population of neurons contribute to the encoding of information.To address these questions, simultaneous multi-unit extracellular recordings were made in vivo in the locust brain. The first part of the dissertation describes several advances in spike-sorting methods that were necessary for analyzing such recordings. These advances include quantitative tests of sorting quality, and they allow for automated spike-sorting. Using these techniques, data sampled from tens of neurons over hours of recording can be analyzed with relative ease.The remainder of the dissertation examines the encoding of olfactory information by a population of neurons called projection neurons (PNs), located in the first olfactory relay of the brain. Odor information is shown to be represented by a subpopulation of responsive PNs. The composition of this population changes over time in an odor-specific manner, thus forming a distributed, dynamical representation. The statistics of this response and its dynamics are quantified.Furthermore, the mechanism by which odor information is extracted from the PN population response is examined. A second set of recordings were made from Kenyon cells (KCs), which receive direct excitatory synaptic input from PNs. The dynamic response of the PN population appears to be decoded by KCs through a mechanism based on several underlying components, including oscillatory dynamics, feed-forward inhibition, and intrinsic properties of the KCs. This decoding process is shown to drastically change the odor representations, from dense to sparse.Taken together, the results presented in this dissertation establish that the complex spatial and temporal dynamics of the PN population do encode odor information, and that this information is decoded by other neurons (KCs) in a very precise way, resulting in a drastic transformation of representation. The basic mechanisms underlying this transformation exist in many brain areas and across phyla, suggesting that many of the principles described here could be of general relevance.

In the insect olfactory system, oscillatory synchronization is functionally relevant and reflects the coherent activation of dynamic neural assemblies. We examined the role of such oscillatory synchronization in information transfer between networks in this system. The antennal lobe is the obligatory relay for olfactory afferent signals and generates oscillatory output. The mushroom body is responsible for formation and retrieval of olfactory and other memories. The format of odor representations differs significantly across these structures. Whereas representations are dense, dynamic, and seemingly redundant in the antennal lobe, they are sparse and carried by more selective neurons in the mushroom body. This transformation relies on a combination of oscillatory dynamics and intrinsic and circuit properties that act together to selectively filter and synthesize the output from the antennal lobe. These results provide direct support for the functional relevance of correlation codes and shed some light on the role of oscillatory synchronization in sensory networks.

We have developed a simple and expandable procedure for classification and validation of extracellular data based on a probabilistic model of data generation. This approach relies on an empirical characterization of the recording noise. We first use this noise characterization to optimize the clustering of recorded events into putative neurons. As a second step, we use the noise model again to assess the quality of each cluster by comparing the within-cluster variability to that of the noise. This second step can be performed independently of the clustering algorithm used, and it provides the user with quantitative as well as visual tests of the quality of the classification.