Prominent lateral spread of imaged evoked activity beyond cortical columns in barrel cortex provides foundation for coding whisker identity.

The posterior medial barrel subfield (PMBSF) of a rat primary somatosensory cortex exquisitely demonstrates topography and columnar organization, defining features of sensory cortices in the mammalian brain. Optical imaging and neuronal recordings in rat PMBSF demonstrate how evoked cortical activity following single whisker stimulation also rapidly spreads laterally into surrounding cortices, disregarding columnar and modality boundaries. The current study quantifies the spatial prominence of such lateral activity spreads by demonstrating that functional connectivity between laterally spaced cortical locations is actually stronger than between vertically spaced cortical locations. Further, the total amount of evoked activity within and beyond single column boundaries was quantified based on intrinsic signal optical imaging, single units and local field potentials recordings, revealing that the vast majority of whisker evoked activity in PMBSF occurs beyond columnar boundaries. Finally, a simple two-layer artificial neural network model of PMBSF demonstrates the capacity of extracolumnar evoked activity spread to provide a foundation for accurate whisker stimulus classification that is robust to random scaling of inputs and local noise. Indeed, classification performance improved when more of the lateral spread was included in the model, providing further evidence for the relevance of the lateral spread.

Imaging Cajal's neuronal avalanche: how wide-field optical imaging of the point-spread advanced the understanding of neocortical structure-function relationship.

This review brings together a collection of studies that specifically use wide-field high-resolution mesoscopic level imaging techniques (intrinsic signal optical imaging; voltage-sensitive dye optical imaging) to image the cortical point spread (PS): the total spread of cortical activation comprising a large neuronal ensemble evoked by spatially restricted (point) stimulation of the sensory periphery (e.g., whisker, pure tone, point visual stimulation). The collective imaging findings, combined with supporting anatomical and electrophysiological findings, revealed some key aspects about the PS including its very large (radius of several mm) and relatively symmetrical spatial extent capable of crossing cytoarchitectural borders and trespassing into other cortical areas; its relationship with underlying evoked subthreshold activity and underlying anatomical system of long-range horizontal projections within gray matter, both also crossing borders; its contextual modulation and plasticity; the ability of its relative spatiotemporal profile to remain invariant to major changes in stimulation parameters; its potential role as a building block for integrative cortical activity; and its ubiquitous presence across various cortical areas and across mammalian species. Together, these findings advance our understanding about the neocortex at the mesoscopic level by underscoring that the cortical PS constitutes a fundamental motif of neocortical structure-function relationship.

Emergence of spatiotemporal invariance in large neuronal ensembles in rat barrel cortex.

Invariant sensory coding is the robust coding of some sensory information (e.g., stimulus type) despite major changes in other sensory parameters (e.g., stimulus strength). The contribution of large populations of neurons (ensembles) to invariant sensory coding is not well understood, but could offer distinct advantages over invariance in single cell receptive fields. To test invariant sensory coding in neuronal ensembles evoked by single whisker stimulation as early as primary sensory cortex, we recorded detailed spatiotemporal movies of evoked ensemble activity through the depth of rat barrel cortex using microelectrode arrays. We found that an emergent property of whisker evoked ensemble activity, its spatiotemporal profile, was notably invariant across major changes in stimulus amplitude (up to >200-fold). Such ensemble-based invariance was found for single whisker stimulation as well as for the integrated profile of activity evoked by the more naturalistic stimulation of the entire whisker array. Further, the integrated profile of whisker array evoked ensemble activity and its invariance to stimulus amplitude shares striking similarities to "funneled" tactile perception in humans. We therefore suggest that ensemble-based invariance could provide a robust neurobiological substrate for invariant sensory coding and integration at an early stage of cortical sensory processing already in primary sensory cortex.

Critical role of the hippocampus in memory for elapsed time.

Episodic memory includes information about how long ago specific events occurred. Since most of our experiences have overlapping elements, remembering this temporal context is crucial for distinguishing individual episodes. The discovery of timing signals in hippocampal neurons, including evidence of "time cells" and of gradual changes in ensemble activity over long timescales, strongly suggests that the hippocampus is important for this capacity. However, behavioral evidence that the hippocampus is critical for the memory of elapsed time is lacking. This is possibly because previous studies have used time durations in the range of seconds when assessing hippocampal dependence, a timescale known to require corticostriatal circuits. Here we developed a nonspatial paradigm to test the hypothesis that the hippocampus is critical for keeping track of elapsed time over several minutes. We report that rats have a robust ability to remember durations at this timescale. We then determined the role of the hippocampus using infusions of fluorophore-conjugated muscimol, a GABAA agonist. We found that the hippocampus was essential for discriminating smaller, but not larger, temporal differences (measured in log units), consistent with a role in temporal pattern separation. Importantly, this effect was observed at long (minutes) but not short (seconds) timescales, suggesting an interplay of temporal resolution and timescale in determining hippocampal dependence. These results offer compelling evidence that the hippocampus plays a critical role in remembering how long ago events occurred.

Whisker array functional representation in rat barrel cortex: transcendence of one-to-one topography and its underlying mechanism.

The one-to-one relationship between whiskers, barrels, and barrel columns described for rat barrel cortex demonstrates that the organization of cortical function adheres to topographical and columnar principles. Supporting evidence is typically based on a single or few whiskers being stimulated, although behaving rats rely on the use of all their whiskers. Less is known about the cortical response when many whiskers are stimulated. Here, we use intrinsic signal optical imaging and supra- and sub-threshold electrophysiology recordings to map and characterize the cortical response to an array of all large whiskers. The cortical response was found to possess a single peak located centrally within a large activation spread, thereby no longer conveying information about the individual identities of the stimulated whiskers (e.g., many local peaks). Using modeling and pharmacological manipulations, we determined that this single central peak, plus other salient properties, can be predicted by and depends on large cortical activation spreads evoked by individual whisker stimulation. Compared to single whisker stimulation, the peak magnitude was comparable in strength and the response area was 2.6-fold larger, with both exhibiting a reduction in variability that was particularly pronounced (3.8x) for the peak magnitude. Findings extended to a different collection (subset) of whiskers. Our results indicate the rat barrel cortex response to multi-site stimulation transcends one-to-one topography to culminate in a large activation spread with a single central peak, and offer a potential neurobiological mechanism for the psychophysical phenomenon of multi-site stimulation being perceived as though a single, central site has been stimulated.

Electrical synapses control hippocampal contributions to fear learning and memory.

The role of electrical synapses in synchronizing neuronal assemblies in the adult mammalian brain is well documented. However, their role in learning and memory processes remains unclear. By combining Pavlovian fear conditioning, activity-dependent immediate early gene expression, and in vivo electrophysiology, we discovered that blocking neuronal gap junctions within the dorsal hippocampus impaired context-dependent fear learning, memory, and extinction. Theta rhythms in freely moving rats were also disrupted. Our results show that gap junction-mediated neuronal transmission is a prominent feature underlying emotional memories.

The accurate measurement of fear memory in Pavlovian conditioning: Resolving the baseline issue.

Fear conditioning has become an indispensable behavioral task in an increasingly vast array of research disciplines. Yet one unresolved issue is how conditional fear to an explicit cue interacts with and is potentially confounded by fear prior to tone presentation, referred to as baseline fear. After tone-shock pairings, we experimentally manipulated baseline fear by presenting unpaired shocks in the testing chamber and then analyzed the accuracy of common methods for reporting tone fear. Our findings indicate that baseline fear and tone fear tend to interact, where freezing to the tone increases as baseline fear increases. However, the form of interaction is not linear across all conditions and none of the commonly used reporting methods were consistently able to eliminate the confounding effects of baseline fear. We propose a methodological solution in which baseline fear is reduced to very low levels by first extinguishing fear to the training context and then pre-exposing to the testing context.