Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). This device samples neuronal activity at ultra-high spatial density (~10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron's electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ~3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior.

Dissociation between Postrhinal Cortex and Downstream Parahippocampal Regions in the Representation of Egocentric Boundaries.

Navigation requires the integration of many sensory inputs to form a multi-modal cognitive map of the environment, which is believed to be implemented in the hippocampal region by spatially tuned cells [1-10]. These cells encode various aspects of the environment in a world-based (allocentric) reference frame. Although the cognitive map is represented in allocentric coordinates, the environment is sensed through diverse sensory organs, mostly situated in the animal's head, and therefore represented in sensory and parietal cortices in head-centered egocentric coordinates. Yet it is not clear how and where the brain transforms these head-centered egocentric representations to map-like allocentric representations computed in the hippocampal region. Theoretical modeling has predicted a role for both egocentric and head direction (HD) information in performing an egocentric-allocentric transformation [11-15]. Here, we recorded new data and also used data from a previous study [16]. Adapting a generalized linear model (GLM) classification [17]; we show that the postrhinal cortex (POR) contains a population of pure egocentric boundary cells (EBCs), in contrast with the conjunctive EBCs × HD cells, which we found downstream mostly in the parasubiculum (PaS) and in the medial entorhinal cortex (MEC). Our finding corroborates the idea of a brain network performing an egocentric to allocentric transformation by HD cells. This is a fundamental building block in the formation of the brain's internal cognitive map.

Role of the head-direction signal in spatial tasks: when and how does it guide behavior?

Since their discovery, mammalian head-direction (HD) cells have been extensively researched in terms of sensory origins, external cue control, and circuitry. However, the relationship of HD cells to behavior is not yet fully understood. In the current review, we examine the anatomical clues for information flow in the HD circuit and an emerging body of evidence that links neural activity of HD cells and spatial orientation. We hypothesize from results obtained in spatial orientation tasks involving HD cells that when properly aligned with available external cues, the HD signal could be used for guiding rats to a goal location. However, contradictory inputs from separate sensory systems may reduce the influence of the HD signal such that animals are able to switch between this and other systems according to their impact on behavior.

Consistency of Spatial Representations in Rat Entorhinal Cortex Predicts Performance in a Reorientation Task.

Goal-directed behavior can be affected by environmental geometry. A classic example is the rectangular arena reorientation task, where subjects commonly confuse opposite but geometrically identical corners [1]. Until recently, little was known about how environmental geometry shapes spatial representations in a neurobehavioral context [2] (although see [3]). In the present study, we asked: Under what circumstances does the internal cognitive map predict behavior? And when does it fail to do so? To this end, we developed a variant of the classical reorientation task that allows for investigation of temporal dynamics of reorientation. We recorded head-direction (HD) cells and grid cells in the medial entorhinal cortex (MEC) of rats before, during, and after performing the task. MEC cells showed a bimodal response of being either aligned or rotated, relative to the free-foraging open-field sessions. Alignment was remarkably stable between disorientations and indicative of corner choice as a function of current and past alignment of spatial representations. Accordingly, when the cells showed consistent and properly aligned readout across multiple trials, behavioral choices were better predicted by HD and grid cell readout, with a probability of more than 70%. This was not the case when the cells did not show a stable consistent readout. Our findings indicate that entorhinal spatial representations predict corner choice, contingent on the stability and reliability of their readout. This work sets the stage for further studies on the link between the reliability of the neuronal signal and behavior, with implications for many brain systems in many organisms.

Network analysis of rat spatial cognition: behaviorally-established symmetry in a physically asymmetrical environment.

BACKGROUND: We set out to solve two inherent problems in the study of animal spatial cognition (i) What is a "place"?; and (ii) whether behaviors that are not revealed as differing by one methodology could be revealed as different when analyzed using a different approach. METHODOLOGY: We applied network analysis to scrutinize spatial behavior of rats tested in either a symmetrical or asymmetrical layout of 4, 8, or 12 objects placed along the perimeter of a round arena. We considered locations as the units of the network (nodes), and passes between locations as the links within the network. PRINCIPAL FINDINGS: While there were only minor activity differences between rats tested in the symmetrical or asymmetrical object layouts, network analysis revealed substantial differences. Viewing 'location' as a cluster of stopping coordinates, the key locations (large clusters of stopping coordinates) were at the objects in both layouts with 4 objects. However, in the asymmetrical layout with 4 objects, additional key locations were spaced by the rats between the objects, forming symmetry among the key locations. It was as if the rats had behaviorally imposed symmetry on the physically asymmetrical environment. Based on a previous finding that wayfinding is easier in symmetrical environments, we suggest that when the physical attributes of the environment were not symmetrical, the rats established a symmetric layout of key locations, thereby acquiring a more legible environment despite its complex physical structure. CONCLUSIONS AND SIGNIFICANCE: The present study adds a behavioral definition for "location", a term that so far has been mostly discussed according to its physical attributes or neurobiological correlates (e.g.--place and grid neurons). Moreover, network analysis enabled the assessment of the importance of a location, even when that location did not display any distinctive physical properties.