Entorhinal cortical delta oscillations drive memory consolidation.

Long-term memories are formed by creating stable memory representations via memory consolidation, which mainly occurs during sleep following the encoding of labile memories in the hippocampus during waking. The entorhinal cortex (EC) has intricate connections with the hippocampus, but its role in memory consolidation is largely unknown. Using cell-type- and input-specific in vivo neural activity recordings, here we show that the temporoammonic pathway neurons in the EC, which directly innervate the output area of the hippocampus, exhibit potent oscillatory activities during anesthesia and sleep. Using in vivo individual and populational neuronal activity recordings, we demonstrate that a subpopulation of the temporoammonic pathway neurons, which we termed sleep cells, generate delta oscillations via hyperpolarization-activated cyclic-nucleotide-gated channels during sleep. The blockade of these oscillations significantly impaired the consolidation of hippocampus-dependent memory. Together, our findings uncover a key driver of delta oscillations and memory consolidation that are found in the EC.

Gigapixel imaging with a novel multi-camera array microscope.

The dynamics of living organisms are organized across many spatial scales. However, current cost-effective imaging systems can measure only a subset of these scales at once. We have created a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution recording from multiple spatial scales simultaneously, ranging from structures that approach the cellular scale to large-group behavioral dynamics. By collecting data from up to 96 cameras, we computationally generate gigapixel-scale images and movies with a field of view over hundreds of square centimeters at an optical resolution of 18 µm. This allows us to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales, including larval zebrafish, fruit flies, nematodes, carpenter ants, and slime mold. Further, the MCAM architecture allows stereoscopic tracking of the z-position of organisms using the overlapping field of view from adjacent cameras. Overall, by removing the bottlenecks imposed by single-camera image acquisition systems, the MCAM provides a powerful platform for investigating detailed biological features and behavioral processes of small model organisms across a wide range of spatial scales.

Whole-brain interactions underlying zebrafish behavior.

Detailed quantification of neural dynamics across the entire brain will be the key to genuinely understanding perception and behavior. With the recent developments in microscopy and biosensor engineering, the zebrafish has made a grand entrance in neuroscience as its small size and optical transparency enable imaging access to its entire brain at cellular and even subcellular resolution. However, until recently many neurobiological insights were largely correlational or provided little mechanistic insight into the brain-wide population dynamics generated by diverse types of neurons. Now with increasingly sophisticated behavioral, imaging, and causal intervention paradigms, zebrafish are revealing how entire vertebrate brains function. Here we review recent research that fulfills promises made by the early wave of technical advances. These studies reveal new features of brain-wide neural processing and the importance of integrative investigation and computational modelling. Moreover, we outline the future tools necessary for solving broader brain-scale circuit problems.

Cortical Neuroprosthesis Merges Visible and Invisible Light Without Impairing Native Sensory Function.

Adult rats equipped with a sensory prosthesis, which transduced infrared (IR) signals into electrical signals delivered to somatosensory cortex (S1), took approximately 4 d to learn a four-choice IR discrimination task. Here, we show that when such IR signals are projected to the primary visual cortex (V1), rats that are pretrained in a visual-discrimination task typically learn the same IR discrimination task on their first day of training. However, without prior training on a visual discrimination task, the learning rates for S1- and V1-implanted animals converged, suggesting there is no intrinsic difference in learning rate between the two areas. We also discovered that animals were able to integrate IR information into the ongoing visual processing stream in V1, performing a visual-IR integration task in which they had to combine IR and visual information. Furthermore, when the IR prosthesis was implanted in S1, rats showed no impairment in their ability to use their whiskers to perform a tactile discrimination task. Instead, in some rats, this ability was actually enhanced. Cumulatively, these findings suggest that cortical sensory neuroprostheses can rapidly augment the representational scope of primary sensory areas, integrating novel sources of information into ongoing processing while incurring minimal loss of native function.

Embedding a Panoramic Representation of Infrared Light in the Adult Rat Somatosensory Cortex through a Sensory Neuroprosthesis.

Can the adult brain assimilate a novel, topographically organized, sensory modality into its perceptual repertoire? To test this, we implemented a microstimulation-based neuroprosthesis that rats used to discriminate among infrared (IR) light sources. This system continuously relayed information from four IR sensors that were distributed to provide a panoramic view of IR sources, into primary somatosensory cortex (S1). Rats learned to discriminate the location of IR sources in <4 d. Animals in which IR information was delivered in spatial register with whisker topography learned the task more quickly. Further, in animals that had learned to use the prosthesis, altering the topographic mapping from IR sensor to stimulating electrode had immediate deleterious effects on discrimination performance. Multielectrode recordings revealed that S1 neurons had multimodal (tactile/IR) receptive fields, with clear preferences for those stimuli most likely to be delivered during the task. Neuronal populations predicted, with high accuracy, which stimulation pattern was present in small (75 ms) time windows. Surprisingly, when identical microstimulation patterns were delivered during an unrelated task, cortical activity in S1 was strongly suppressed. Overall, these results show that the adult mammalian neocortex can readily absorb completely new information sources into its representational repertoire, and use this information in the production of adaptive behaviors.

Basal forebrain dynamics during a tactile discrimination task.

The nucleus basalis (NB) is a cholinergic neuromodulatory structure that projects liberally to the entire cortical mantle and regulates information processing in all cortical layers. Here, we recorded activity from populations of single units in the NB as rats performed a whisker-dependent tactile discrimination task. Over 80% of neurons responded with significant modulation in at least one phase of the task. Such activity started before stimulus onset and continued for seconds after reward delivery. Firing rates monotonically increased with reward magnitude during the task, suggesting that NB neurons are not indicating the absolute deviation from expected reward amounts. Individual neurons also encoded significant amounts of information about stimulus identity. Such robust coding was not present when the same stimuli were delivered to lightly anesthetized animals, suggesting that the NB neurons contain a sensorimotor, rather than purely sensory or motor, representation of the environment. Overall, these results support the hypothesis that neurons in the NB provide a value-laden representation of the sensorimotor state of the animal as it engages in significant behavioral tasks.

Lightning injuries in sports and recreation.

The powers of lightning have been worshiped and feared by all known human cultures. While the chance of being struck by lightning is statistically very low, that risk becomes much greater in those who frequently work or play outdoors. Over the past 2 yr, there have been nearly 50 lightning-related deaths reported within the United States, with a majority of them associated with outdoor recreational activities. Recent publications primarily have been case studies, review articles, and a discussion of a sixth method of injury. The challenge in reducing lightning-related injuries in organized sports has been addressed well by both the National Athletic Trainers' Association and the National Collegiate Athletic Association in their guidelines on lightning safety. Challenges remain in educating the general population involved in recreational outdoor activities that do not fall under the guidelines of organized sports.

Perceiving invisible light through a somatosensory cortical prosthesis.

Sensory neuroprostheses show great potential for alleviating major sensory deficits. It is not known, however, whether such devices can augment the subject's normal perceptual range. Here we show that adult rats can learn to perceive otherwise invisible infrared light through a neuroprosthesis that couples the output of a head-mounted infrared sensor to their somatosensory cortex (S1) via intracortical microstimulation. Rats readily learn to use this new information source, and generate active exploratory strategies to discriminate among infrared signals in their environment. S1 neurons in these infrared-perceiving rats respond to both whisker deflection and intracortical microstimulation, suggesting that the infrared representation does not displace the original tactile representation. Hence, sensory cortical prostheses, in addition to restoring normal neurological functions, may serve to expand natural perceptual capabilities in mammals.

Changes in S1 neural responses during tactile discrimination learning.

In freely moving rats that are actively performing a discrimination task, single-unit responses in primary somatosensory cortex (S1) are strikingly different from responses to comparable tactile stimuli in immobile rats. For example, in the active discrimination context prestimulus response modulations are common, responses are longer in duration and more likely to be inhibited. To determine whether these differences emerge as rats learned a whisker-dependent discrimination task, we recorded single-unit S1 activity while rats learned to discriminate aperture-widths using their whiskers. Even before discrimination training began, S1 responses in freely moving rats showed many of the signatures of active responses, such as increased duration of response and prestimulus response modulations. As rats subsequently learned the discrimination task, single unit responses changed: more cortical units responded to the stimuli, neuronal sensory responses grew in duration, and individual neurons better predicted aperture-width. In summary, the operant behavioral context changes S1 tactile responses even in the absence of tactile discrimination, whereas subsequent width discrimination learning refines the S1 representation of aperture-width.

Encoding and decoding touch location in the leech CNS.

Spike times encode stimulus values in many sensory systems, but it is generally unknown whether such temporal variations are decoded (i.e., whether they influence downstream networks that control behavior). In the present study, we directly address this decoding problem by quantifying both sensory encoding and decoding in the leech. By mechanically stimulating the leech body wall while recording from mechanoreceptors, we show that pairs of leech sensory neurons with overlapping receptive fields encode touch location by their relative latencies, number of spikes, and instantaneous firing rates, with relative latency being the most accurate indicator of touch location. We then show that the relative latency and count are decoded by manipulating these variables in sensory neuron pairs while simultaneously monitoring the resulting behavior. Although both variables are important determinants of leech behavior, the decoding mechanisms are more sensitive to changes in relative spike count than changes in relative latency.

Quantifying stimulus discriminability: a comparison of information theory and ideal observer analysis.

Performance in sensory discrimination tasks is commonly quantified using either information theory or ideal observer analysis. These two quantitative frameworks are often assumed to be equivalent. For example, higher mutual information is said to correspond to improved performance of an ideal observer in a stimulus estimation task. To the contrary, drawing on and extending previous results, we show that five information-theoretic quantities (entropy, response-conditional entropy, specific information, equivocation, and mutual information) violate this assumption. More positively, we show how these information measures can be used to calculate upper and lower bounds on ideal observer performance, and vice versa. The results show that the mathematical resources of ideal observer analysis are preferable to information theory for evaluating performance in a stimulus discrimination task. We also discuss the applicability of information theory to questions that ideal observer analysis cannot address.

Location and intensity discrimination in the leech local bend response quantified using optic flow and principal components analysis.

In response to touches to their skin, medicinal leeches shorten their body on the side of the touch. We elicited local bends by delivering precisely controlled pressure stimuli at different locations, intensities, and durations to body-wall preparations. We video-taped the individual responses, quantifying the body-wall displacements over time using a motion-tracking algorithm based on making optic flow estimates between video frames. Using principal components analysis (PCA), we found that one to three principal components fit the behavioral data much better than did previous (cosine) measures. The amplitudes of the principal components (i.e., the principal component scores) nicely discriminated the responses to stimuli both at different locations and of different intensities. Leeches discriminated (i.e., produced distinguishable responses) between touch locations that are approximately a millimeter apart. Their ability to discriminate stimulus intensity depended on stimulus magnitude: discrimination was very acute for weak stimuli and less sensitive for stronger stimuli. In addition, increasing the stimulus duration improved the leech's ability to discriminate between stimulus intensities. Overall, the use of optic flow fields and PCA provide a powerful framework for characterizing the discrimination abilities of the leech local bend response.

Transit of rat uterine stromal cells through G1 phase of the cell cycle requires temporal and cell-specific hormone-dependent changes on cell cycle regulators.

Progesterone pretreatment increases the number of synchronously proliferating stromal cells in the ovariectomized rat uterus, but estrogen is necessary to stimulate reentry into the cell cycle. To investigate the mechanisms underlying differential hormone actions, sexually mature ovariectomized rats were injected with progesterone (2 mg) for three consecutive days. Estradiol 17-beta (0.6 microg) was administered to initiate cell proliferation. Uterine samples were collected at timed intervals. Cell entry into DNA replication was monitored by injecting 5-bromo-2'-deoxyuridine (1 mg/100 g body weight) 2 h before necropsy. Demicolchicine (400 microg) was injected 30 min before necropsy to assess transit into M phase. Temporal progress through G1 was determined by spatial changes in cyclin D1/D3 proteins. Total cyclin D1/D3 protein and mRNA was measured by Western and Northern blotting. Estrogen increased the number of 5-bromo-2'-deoxyuridine-positive stromal cells (P < 0.05), compared with the number in rats treated with progesterone alone. An increase (P < 0.05) in the number of M-phase cells occurred at 12 h post estrogen. There was no evidence for epithelial cell proliferation in response to steroid treatments. Cyclin D1/D3 mRNA was expressed in the uteri of ovariectomized and hormone treated rats. The D-type cyclin proteins, however, were not evident in stromal cells without estrogen treatment. Progesterone pretreatment inhibited estrogen-dependent epithelial cell proliferation while redirecting D-type cyclin expression to the uterine stroma. Stromal cell transit through G1 required nongenomic steroid-dependent action on signal transduction pathways that control the nuclear localization and cell type-specific expression of the D-type cyclin proteins.

Facial deformities: assessment and treatment planning with computers

Using standardised anatomical landmarks in the skull, face and jaws, a new computerised cephalometric analysis technique is described to assess facial form. The result of a preliminary pilot study designed to identify ethnic differences in facial form are presented. (AU)

Cleft lip and palate experience in Trinidad and Tobago

The results of a preliminary survey to investigate the prevalence of the cleft lip and palate deformity in Trinidad and Tobago are presented. Sources and data collection are described, with recommendations for improving the overall clinical management of these unfortunate children. (AU)