A platform for semiautomated voluntary training of common marmosets for behavioral neuroscience.

Generally behavioral neuroscience studies of the common marmoset employ adaptations of well-established training methods used with macaque monkeys. However, in many cases these approaches do not readily generalize to marmosets indicating a need for alternatives. Here we present the development of one such alternate: a platform for semiautomated, voluntary in-home cage behavioral training that allows for the study of naturalistic behaviors. We describe the design and production of a modular behavioral training apparatus using CAD software and digital fabrication. We demonstrate that this apparatus permits voluntary behavioral training and data collection throughout the marmoset's waking hours with little experimenter intervention. Furthermore, we demonstrate the use of this apparatus to reconstruct the kinematics of the marmoset's upper limb movement during natural foraging behavior.NEW & NOTEWORTHY The study of marmosets in neuroscience has grown rapidly and presents unique challenges. We address those challenges with an innovative platform for semiautomated, voluntary training that allows marmosets to train throughout their waking hours with minimal experimenter intervention. We describe the use of this platform to capture upper limb kinematics during foraging and to expand the opportunities for behavioral training beyond the limits of traditional training sessions. This flexible platform can easily incorporate other tasks.

Multiplexed Population Coding of Stimulus Properties by Leech Mechanosensory Cells.

Sensory coding has long been discussed in terms of a dichotomy between spike timing and rate coding. However, recent studies found that in primate mechanoperception and other sensory systems, spike rates and timing of cell populations complement each other. They simultaneously carry information about different stimulus properties in a multiplexed way. Here, we present evidence for multiplexed encoding of tactile skin stimulation in the tiny population of leech mechanoreceptors, consisting of only 10 cells of two types with overlapping receptive fields. Each mechanoreceptor neuron of the leech varies spike count and response latency to both touch intensity and location, leading to ambiguous responses to different stimuli. Nevertheless, three different stimulus estimation techniques consistently reveal that the neuronal population allows reliable decoding of both stimulus properties. For the two mechanoreceptor types, the transient responses of T (touch) cells and the sustained responses of P (pressure) cells, the relative timing of the first spikes of two mechanoreceptors encodes stimulus location, whereas summed spike counts represent touch intensity. Differences between the cell types become evident in responses to combined stimulus properties. The best estimation performance for stimulus location is obtained from the relative first spike timing of the faster and temporally more precise T cells. Simultaneously, the sustained responses of P cells indicate touch intensity by summed spike counts and stimulus duration by the duration of spike responses. The striking similarities of these results with previous findings on primate mechanosensory afferents suggest multiplexed population coding as a general principle of somatosensation. SIGNIFICANCE STATEMENT: Multiplexing, the simultaneous encoding of different stimulus properties by distinct neuronal response features, has recently been suggested as a mechanism used in several sensory systems, including primate somatosensation. While a rigorous experimental verification of the multiplexing hypothesis is difficult to accomplish in a complex vertebrate system, it is feasible for a small population of individually characterized leech neurons. Monitoring the responses of all four mechanoreceptors innervating a patch of skin revealed striking similarities between touch encoding in the primate and the leech: summed spike counts represent stimulus intensity, whereas relative timing of first spikes encodes stimulus location. These findings suggest that multiplexed population coding is a general mechanism of touch encoding common to species as different as man and worm.

Chronic wireless neural population recordings with common marmosets.

Marmosets are an increasingly important model system for neuroscience in part due to genetic tractability and enhanced cortical accessibility, due to a lissencephalic neocortex. However, many of the techniques generally employed to record neural activity in primates inhibit the expression of natural behaviors in marmosets precluding neurophysiological insights. To address this challenge, we have developed methods for recording neural population activity in unrestrained marmosets across multiple ethological behaviors, multiple brain states, and over multiple years. Notably, our flexible methodological design allows for replacing electrode arrays and removal of implants providing alternative experimental endpoints. We validate the method by recording sensorimotor cortical population activity in freely moving marmosets across their natural behavioral repertoire and during sleep.

Effects of Touch Location and Intensity on Interneurons of the Leech Local Bend Network.

Touch triggers highly precise behavioural responses in the leech. The underlying network of this so-called local bend reflex consists of three layers of individually characterised neurons. While the population of mechanosensory cells provide multiplexed information about the stimulus, not much is known about how interneurons process this information. Here, we analyse the responses of two local bend interneurons (cell 157 and 159) to a mechanical stimulation of the skin and show their response characteristics to naturalistic stimuli. Intracellular dye-fills combined with structural imaging revealed that these interneurons are synaptically coupled to all three types of mechanosensory cells (T, P, and N cells). Since tactile stimulation of the skin evokes spikes in one to two cells of each of the latter types, interneurons combine inputs from up to six mechanosensory cells. We find that properties of touch location and intensity can be estimated reliably and accurately based on the graded interneuron responses. Connections to several mechanosensory cell types and specific response characteristics of the interneuron types indicate specialised filter and integration properties within this small neuronal network, thus providing evidence for more complex signal processing than previously thought.

Encoding of Tactile Stimuli by Mechanoreceptors and Interneurons of the Medicinal Leech.

For many animals processing of tactile information is a crucial task in behavioral contexts like exploration, foraging, and stimulus avoidance. The leech, having infrequent access to food, developed an energy efficient reaction to tactile stimuli, avoiding unnecessary muscle movements: The local bend behavior moves only a small part of the body wall away from an object touching the skin, while the rest of the animal remains stationary. Amazingly, the precision of this localized behavioral response is similar to the spatial discrimination threshold of the human fingertip, although the leech skin is innervated by an order of magnitude fewer mechanoreceptors and each midbody ganglion contains only 400 individually identified neurons in total. Prior studies suggested that this behavior is controlled by a three-layered feed-forward network, consisting of four mechanoreceptors (P cells), approximately 20 interneurons and 10 individually characterized motor neurons, all of which encode tactile stimulus location by overlapping, symmetrical tuning curves. Additionally, encoding of mechanical force was attributed to three types of mechanoreceptors reacting to distinct intensity ranges: T cells for touch, P cells for pressure, and N cells for strong, noxious skin stimulation. In this study, we provide evidences that tactile stimulus encoding in the leech is more complex than previously thought. Combined electrophysiological, anatomical, and voltage sensitive dye approaches indicate that P and T cells both play a major role in tactile information processing resulting in local bending. Our results indicate that tactile encoding neither relies on distinct force intensity ranges of different cell types, nor location encoding is restricted to spike count tuning. Instead, we propose that P and T cells form a mixed type population, which simultaneously employs temporal response features and spike counts for multiplexed encoding of touch location and force intensity. This hypothesis is supported by our finding that previously identified local bend interneurons receive input from both P and T cells. Some of these interneurons seem to integrate mechanoreceptor inputs, while others appear to use temporal response cues, presumably acting as coincidence detectors. Further voltage sensitive dye studies can test these hypotheses how a tiny nervous system performs highly precise stimulus processing.