Adaptation supports short-term memory in a visual change detection task.

The maintenance of short-term memories is critical for survival in a dynamically changing world. Previous studies suggest that this memory can be stored in the form of persistent neural activity or using a synaptic mechanism, such as with short-term plasticity. Here, we compare the predictions of these two mechanisms to neural and behavioral measurements in a visual change detection task. Mice were trained to respond to changes in a repeated sequence of natural images while neural activity was recorded using two-photon calcium imaging. We also trained two types of artificial neural networks on the same change detection task as the mice. Following fixed pre-processing using a pretrained convolutional neural network, either a recurrent neural network (RNN) or a feedforward neural network with short-term synaptic depression (STPNet) was trained to the same level of performance as the mice. While both networks are able to learn the task, the STPNet model contains units whose activity are more similar to the in vivo data and produces errors which are more similar to the mice. When images are omitted, an unexpected perturbation which was absent during training, mice often do not respond to the omission but are more likely to respond to the subsequent image. Unlike the RNN model, STPNet produces a similar pattern of behavior. These results suggest that simple neural adaptation mechanisms may serve as an important bottom-up memory signal in this task, which can be used by downstream areas in the decision-making process.

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.

Characterization of Learning, Motivation, and Visual Perception in Five Transgenic Mouse Lines Expressing GCaMP in Distinct Cell Populations.

To study the mechanisms of perception and cognition, neural measurements must be made during behavior. A goal of the Allen Brain Observatory is to map the activity of distinct cortical cell classes underlying visual and behavioral processing. Here we describe standardized methodology for training head-fixed mice on a visual change detection task, and we use our paradigm to characterize learning and behavior of five GCaMP6-expressing transgenic lines. We used automated training procedures to facilitate comparisons across mice. Training times varied, but most transgenic mice learned the behavioral task. Motivation levels also varied across mice. To compare mice in similar motivational states we subdivided sessions into over-, under-, and optimally motivated periods. When motivated, the pattern of perceptual decisions were highly correlated across transgenic lines, although overall performance (d-prime) was lower in one line labeling somatostatin inhibitory cells. These results provide important context for using these mice to map neural activity underlying perception and behavior.

Experience shapes activity dynamics and stimulus coding of VIP inhibitory cells.

Cortical circuits can flexibly change with experience and learning, but the effects on specific cell types, including distinct inhibitory types, are not well understood. Here we investigated how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned a visual change detection task with a set of eight natural scene images. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three sets of novel images. Strikingly, the temporal dynamics of VIP activity differed markedly between novel and familiar images: VIP cells were stimulus-driven by novel images but were suppressed by familiar stimuli and showed ramping activity when expected stimuli were omitted from a temporally predictable sequence. This prominent change in VIP activity suggests that these cells may adopt different modes of processing under novel versus familiar conditions.

Effects of anesthesia with nitrous oxide on tympanoplasty outcomes: a randomized controlled trial.

OBJECTIVES: To investigate effects of nitrous oxide (N2O), as inhalational anesthetic agent, on tympanoplasty outcomes. METHODS: In this randomized controlled trial, patients were randomized into two groups: 39 patients who received N2O as an inhalant anesthesia and 47 patients who did not receive. All were operated on with standard type of ear surgery. The protocol for the two groups was identical. Before surgery baseline audiometry was performed. Postoperative audiological controls were carried out at 3 months. RESULTS: There was no statistically significant difference between two groups regarding graft outcomes. No significant differences were found between the two groups regarding air-bone gap or bone conduction hearing level. CONCLUSIONS: Nitrous oxide usage does not seem to have significant impact on graft or hearing outcome of patients undergoing surgical repair of tympanic membrane.

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines.

Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

What Motivates Talented Medical Students to Study Simultaneously at Master of Public Health (MPH)?

BACKGROUND: Nearly three decades ago, the Master of Public Health (MPH) academic degree was introduced to Tehran University of Medical Sciences' School of Public Health, Tehran, Iran. A new program for simultaneous education of medical, pharmaceutical and dental students was initiated in 2006. Talented students had the opportunity to study MPH simultaneously. There were some concerns about this kind of admission; as to whether these students who were not familiar with the health system had the appropriate attitude and background for this field of education. And with the present rate of brain drain, is this just a step towards their immigration without the fulfillment of public health? METHODS: This qualitative study was conducted in 2012 where 26 students took part in focused group discussions and individual interviews. The students were questioned about their motivation and the program's impact on their future career. The participants' statements were analyzed using thematic analysis. RESULTS: THE PRIMARY MOTIVATIONS OF STUDENTS WHO ENTERED THIS PROGRAM WERE: learning health knowledge related issues, gaining a perspective beyond clinical practice, obtaining a degree to strengthen their academic résumé, immigration, learning academic research methods and preparing for the management of health systems in the future. CONCLUSION: Apparently, there was no considerable difference between the motivation of students and the program planners. The students' main motivation for studying MPH was a combination of various interests in research and health sciences issues. Therefore, considering the potential of this group of students, effective academic investment on MPH can have positive impact.