A triple-network organization for the mouse brain.

The triple-network model of psychopathology is a framework to explain the functional and structural neuroimaging phenotypes of psychiatric and neurological disorders. It describes the interactions within and between three distributed networks: the salience, default-mode, and central executive networks. These have been associated with brain disorder traits in patients. Homologous networks have been proposed in animal models, but their integration into a triple-network organization has not yet been determined. Using resting-state datasets, we demonstrate conserved spatio-temporal properties between triple-network elements in human, macaque, and mouse. The model predictions were also shown to apply in a mouse model for depression. To validate spatial homologies, we developed a data-driven approach to convert mouse brain maps into human standard coordinates. Finally, using high-resolution viral tracers in the mouse, we refined an anatomical model for these networks and validated this using optogenetics in mice and tractography in humans. Unexpectedly, we find serotonin involvement within the salience rather than the default-mode network. Our results support the existence of a triple-network system in the mouse that shares properties with that of humans along several dimensions, including a disease condition. Finally, we demonstrate a method to humanize mouse brain networks that opens doors to fully data-driven trans-species comparisons.

Postnatal light alters hypothalamic-pituitary-adrenal axis function and induces a depressive-like phenotype in adult mice.

The postnatal light environment that a mouse experiences during the critical first three postnatal weeks has long-term effects on both its circadian rhythm output and clock gene expression. Furthermore, data from our lab suggest that postnatal light may also impact the hypothalamic-pituitary-adrenal (HPA) axis, which is a key regulator of stress. To test the effect of postnatal light exposure on adult stress responses and circadian rhythmicity, we raised mice under either 24-h light-dark cycles (LD), constant light (LL) or constant dark (DD) during the first three postnatal weeks. After weaning we then exposed all animals to LD cycles (basal conditions), followed by LL (stressed conditions) environments. We examined brain neuropeptide and glucocorticoid receptor (GR) expression, plasma corticosterone concentration rhythm and body temperature rhythm, together with depression- and anxiety-related behaviour. Results showed that LL- and DD-raised mice exhibited decreased GR expression in the hippocampus, increased plasma corticosterone concentration at the onset of the dark phase and a depressive phenotype when exposed to LD cycles later in life. Furthermore, LL-raised mice showed increased corticotrophin-releasing hormone mRNA expression in the paraventricular nucleus of the hypothalamus. When exposed to LL as adults, LL-raised mice showed a significant circadian rhythm of plasma corticosterone concentration, together with a shorter period and stronger circadian rhythm of body temperature compared to DD-raised mice. Taken together, these data suggest that altered postnatal light environments have long-term effects on the HPA axis and the circadian system, which can lead to altered stress responses and a depressive phenotype in adulthood.

Maternal immune activation affects female offspring whisker movements during object exploration in a rat model of neurodevelopmental disorders.

Poly I:C rat offspring are used to investigate the effects of in utero exposure to maternal immune activation (MIA) and have been suggested as a model of neurodevelopmental disorders (NDD). The behavioural symptoms of this model are diverse and can vary with external factors, including the choice of background strain and husbandry practices. Measuring whisker movements provides quantitative, robust measurements of sensory, motor and cognitive behaviours in rodents. In this study, whisker movements were investigated in 50-day-old male and female offspring of MIA-exposed rat dams and compared to age-matched offspring of control (vehicle) dams. Rat offspring were filmed using high-speed videography in a sequential object exploration task with smooth and textured objects. Poly I:C treatment effects were found in female offspring that did not increase whisker mean angular position during object exploration, especially for the smooth object, indicating an attentional deficit. Whisker tracking during object exploration is demonstrated here, for the first time, as a useful, quick and non-invasive tool to identify both treatment effects and sex differences in a model of MIA-induced NDDs.

Melanopsin contributions to irradiance coding in the thalamo-cortical visual system.

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a subset of retinal ganglion cells expressing the photopigment melanopsin (mRGCs). These mRGCs are known to drive such reflex light responses as circadian photoentrainment and pupillomotor movements. By contrast, until now there has been no direct assessment of their contribution to conventional visual pathways. Here, we address this deficit. Using new reporter lines, we show that mRGC projections are much more extensive than previously thought and extend across the dorsal lateral geniculate nucleus (dLGN), origin of thalamo-cortical projection neurons. We continue to show that this input supports extensive physiological light responses in the dLGN and visual cortex in mice lacking rods+cones (a model of advanced retinal degeneration). Moreover, using chromatic stimuli to isolate melanopsin-derived responses in mice with an intact visual system, we reveal strong melanopsin input to the ∼40% of neurons in the LGN that show sustained activation to a light step. We demonstrate that this melanopsin input supports irradiance-dependent increases in the firing rate of these neurons. The implication that melanopsin is required to accurately encode stimulus irradiance is confirmed using melanopsin knockout mice. Our data establish melanopsin-based photoreception as a significant source of sensory input to the thalamo-cortical visual system, providing unique irradiance information and allowing visual responses to be retained even in the absence of rods+cones. These findings identify mRGCs as a potential origin for aspects of visual perception and indicate that they may support vision in people suffering retinal degeneration.

Neural mechanisms underlying psilocybin's therapeutic potential - the need for preclinical in vivo electrophysiology.

Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin's psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin's effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin's net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin's mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin's psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice.

Emotional learning and memory are affected in numerous psychiatric disorders. At a systems level, however, the underlying neural circuitry is not well defined. Rodent fear conditioning (FC) provides a translational model to study the networks underlying associative memory retrieval. In the current study, functional connectivity among regions related to the cue associative fear network were investigated using functional ultrasound (fUS), a novel imaging technique with great potential for detecting neural activity through cerebral blood flow. Behavioral fear expression and fUS imaging were performed one and thirty-one days after FC to assess recent and remote memory recall. Cue-evoked increases in functional connectivity were detected throughout the amygdala, with the lateral (LA) and central (CeA) amygdalar nuclei emerging as major hubs of connectivity, although CeA connectivity was reduced during remote recall. Hippocampal and sensory cortical regions displayed heightened connectivity with the LA during remote recall, whereas interconnectivity between the primary auditory cortex and temporal association areas was reduced. Subregions of the prefrontal cortex exhibited variable changes, where prelimbic connectivity with the amygdala was refined while specific connections between the infralimbic cortex and amygdalar subregions emerged during remote memory retrieval, a signature of extinction memory. Moreover, freezing behavior positively correlated with functional connectivity between hubs of the associative fear network, suggesting that emotional response intensity reflected the strength of the cue-evoked functional network. Overall, our data provide evidence of the functionality of fUS imaging to investigate the neural dynamics of memory retrieval, applicable in the development of innovative treatments for affective disorders.

The lateral entorhinal cortex is a hub for local and global dysfunction in early Alzheimer's disease states.

Functional network activity alterations are one of the earliest hallmarks of Alzheimer's disease (AD), detected prior to amyloidosis and tauopathy. Better understanding the neuronal underpinnings of such network alterations could offer mechanistic insight into AD progression. Here, we examined a mouse model (3xTgAD mice) recapitulating this early AD stage. We found resting functional connectivity loss within ventral networks, including the entorhinal cortex, aligning with the spatial distribution of tauopathy reported in humans. Unexpectedly, in contrast to decreased connectivity at rest, 3xTgAD mice show enhanced fMRI signal within several projection areas following optogenetic activation of the entorhinal cortex. We corroborate this finding by demonstrating neuronal facilitation within ventral networks and synaptic hyperexcitability in projection targets. 3xTgAD mice, thus, reveal a dichotomic hypo-connected:resting versus hyper-responsive:active phenotype. This strong homotopy between the areas affected supports the translatability of this pathophysiological model to tau-related, early-AD deficits in humans.

Timed daily exercise remodels circadian rhythms in mice.

Regular exercise is important for physical and mental health. An underexplored and intriguing property of exercise is its actions on the body's 24 h or circadian rhythms. Molecular clock cells in the brain's suprachiasmatic nuclei (SCN) use electrical and chemical signals to orchestrate their activity and convey time of day information to the rest of the brain and body. To date, the long-lasting effects of regular physical exercise on SCN clock cell coordination and communication remain unresolved. Utilizing mouse models in which SCN intercellular neuropeptide signaling is impaired as well as those with intact SCN neurochemical signaling, we examined how daily scheduled voluntary exercise (SVE) influenced behavioral rhythms and SCN molecular and neuronal activities. We show that in mice with disrupted neuropeptide signaling, SVE promotes SCN clock cell synchrony and robust 24 h rhythms in behavior. Interestingly, in both intact and neuropeptide signaling deficient animals, SVE reduces SCN neural activity and alters GABAergic signaling. These findings illustrate the potential utility of regular exercise as a long-lasting and effective non-invasive intervention in the elderly or mentally ill where circadian rhythms can be blunted and poorly aligned to the external world.

Naturalistic stimulus trains evoke reproducible subicular responses both within and between animals in vivo.

Previous investigation of CA1-evoked subicular responses has used either single low-frequency pulses (LF), paired-pulses (PP), or high-frequency bursts. Here we test for the first time how subiculum responds to naturalistic stimulation trains (NSTs). We recorded CA1-evoked field potentials from dorsal rat subiculum in response to LF, PP, and two NST patterns. The latter were derived from CA1 place cell activity; NST1 contained bursts of stimuli presented in two main episodes, while the burst-patterned stimuli in NST2 were spaced more evenly. NSTs generated significantly greater field responses compared with LF or PP patterns. Response patterns to either NST were significantly correlated across trial repeats in 9 out of 10 rats, supporting a robust postsynaptic encoding of CA1 input by subiculum. Correlations between NST responses were also observed across experiments; however, these were more variable than those within experiments. The relationship between response magnitude and activation history revealed a strong correlation between magnitude and NST instantaneous frequency for NST1 but was weaker for NST2. In addition, the number of stimuli within a prior 500 ms window was a determining factor for response magnitude for both NSTs. Overall, the robust reproducibility in subicular responses within rats suggests that information within NSTs is faithfully transmitted through the CA1-subiculum axis. However, variation in response sequences across rats suggests that encoding patterns to the same input differ across the subiculum. Changes in the ratio of target bursting and regularly spiking neurons along the subicular proximodistal axis may account for this variation. The activation history of this connection also appears to be a strong determining factor for response magnitude.

Quantifying how much attention rodents allocate to motivationally-salient objects with a novel object preference test.

The allocation of attention can be modulated by the emotional value of a stimulus. In order to understand the biasing influence of emotion on attention allocation further, we require an animal test of how motivational salience modulates attention. In mice, female odour triggers arousal and elicits emotional responses in males. Here, we determined the extent to which objects labelled with female odour modulated the attention of C57BL/6J male mice. Seven experiments were conducted, using a modified version of the spontaneous Novel Object Recognition task. Attention was operationalised as differential exploration time of identical objects that were labelled with either female mouse odour (O+), a non-social odour, almond odour (Oa) or not labelled with any odour (O-). In some experiments we tested trial unique (novel) objects than never carried an odour (X-). Using this novel object preference test we found that when single objects were presented, as well as when two objects were presented simultaneously (so competed with each other for attention), O+ received preferential attention compared to O-. This result was independent of whether O+ was at a novel or familiar location. When compared with Oa at a novel location, O+ at a familiar location attracted more attention. Compared to X-, O+ received more exploration only when placed at a novel location, but attention to O+ and X- was equivalent when they were placed in a familiar location. These results suggest that C57BL/6J male mice weigh up aspects of odour, object novelty and special novelty for motivational salience, and that, in some instances, female odour elicits more attention (object exploration) compared to other object properties. The findings of this study pave the way to using motivationally-significant odours to modulate the cognitive processes that give rise to differential attention to objects.

Synaptic biomarker reduction and impaired cognition in the sub-chronic PCP mouse model for schizophrenia.

BACKGROUND: Sub-chronic phencyclidine treatment (scPCP) provides a translational rat model for cognitive impairments associated with schizophrenia (CIAS). CIAS genetic risk factors may be more easily studied in mice; however, CIAS associated biomarker changes are relatively unstudied in the scPCP mouse. AIM: To characterize deficits in object recognition memory and synaptic markers in frontal cortex and hippocampus of the scPCP mouse. METHODS: Female c57/bl6 mice received 10 daily injections of PCP (scPCP; 10 mg/kg, s.c.) or vehicle (n = 8/group). Mice were tested for novel object recognition memory after either remaining in the arena ('no distraction') or being removed to a holding cage ('distraction') during the inter-trial interval. Expression changes for parvalbumin (PV), glutamic acid decarboxylase (GAD67), synaptosomal-associated protein 25 (SNAP-25) and postsynaptic density 95 (PDS95) were measured in frontal cortex, dorsal and ventral hippocampus. RESULTS: scPCP mice showed object memory deficits when distracted by removal from the arena, where they treated previously experienced objects as novel at test. scPCP significantly reduced PV expression in all regions and lower PSD95 levels in frontal cortex and ventral hippocampus. Levels of GAD67 and SNAP-25 were unchanged. CONCLUSIONS: We show for the first time that scPCP mice: (a) can encode and retain object information, but that this memory is susceptible to distraction; (b) display amnesia after distraction; and (c) express reduced PV and PSD95 in frontal cortex and hippocampus. These data further support reductions in PV-dependent synaptic inhibition and NMDAR-dependent glutamatergic plasticity in CIAS and highlight the translational significance of the scPCP mouse.

Constraints on hippocampal processing imposed by the connectivity between CA1, subiculum and subicular targets.

A long-held fundamental function of the rat hippocampus is to provide a spatial map of the environment. The principal hippocampal output region for spatial information is area CA1 and the major target of CA1 is the subiculum. Thus, one possible role of the subiculum is to receive, process and transmit information regarding location to areas outside the hippocampus. Anatomical experiments in the rat have shown that the projections from CA1 to subiculum exist in a series of 'nested loops'. Thus, each part of CA1 does not connect with each part of the subiculum. In turn, the majority of subicular principal neurons at the end of these loops have only one axonal projection target. The identity of these target areas depends on the location of the projecting cell within the subiculum, that is, neurons in different loops (and different septo-temporal levels of the subiculum) project to different sites. Principal neurons in subiculum and CA1 are not highly interconnected, suggesting that spatial information within any one of the nested loops is not shared amongst the others. This anatomical arrangement suggests that spatial information from any one part of CA1 is sent only to the sub-population of subicular principal cells within the same loop. In turn, this sub-population of subicular cells projects information to only a subset of the total range of subicular target areas. Thus, these subicular targets receive spatial information from only a subset of those in CA1. One conclusion from this is that for subicular targets to receive spatial information from the whole environment, area CA1 must have multiple spatial maps, one for each major projection (nested loop) to the subiculum.

Bursting Neurons in the Hippocampal Formation Encode Features of LFP Rhythms.

Burst spike patterns are common in regions of the hippocampal formation such as the subiculum and medial entorhinal cortex (MEC). Neurons in these areas are immersed in extracellular electrical potential fluctuations often recorded as the local field potential (LFP). LFP rhythms within different frequency bands are linked to different behavioral states. For example, delta rhythms are often associated with slow-wave sleep, inactivity and anesthesia; whereas theta rhythms are prominent during awake exploratory behavior and REM sleep. Recent evidence suggests that bursting neurons in the hippocampal formation can encode LFP features. We explored this hypothesis using a two-compartment model of a bursting pyramidal neuron driven by time-varying input signals containing spectral peaks at either delta or theta rhythms. The model predicted a neural code in which bursts represented the instantaneous value, phase, slope and amplitude of the driving signal both in their timing and size (spike number). To verify whether this code is employed in vivo, we examined electrophysiological recordings from the subiculum of anesthetized rats and the MEC of a behaving rat containing prevalent delta or theta rhythms, respectively. In both areas, we found bursting cells that encoded information about the instantaneous voltage, phase, slope and/or amplitude of the dominant LFP rhythm with essentially the same neural code as the simulated neurons. A fraction of the cells encoded part of the information in burst size, in agreement with model predictions. These results provide in-vivo evidence that the output of bursting neurons in the mammalian brain is tuned to features of the LFP.

Phase-locking of bursting neuronal firing to dominant LFP frequency components.

Neuronal firing in the hippocampal formation relative to the phase of local field potentials (LFP) has a key role in memory processing and spatial navigation. Firing can be in either tonic or burst mode. Although bursting neurons are common in the hippocampal formation, the characteristics of their locking to LFP phase are not completely understood. We investigated phase-locking properties of bursting neurons using simulations generated by a dual compartmental model of a pyramidal neuron adapted to match the bursting activity in the subiculum of a rat. The model was driven with stochastic input signals containing a power spectral profile consistent with physiologically relevant frequencies observed in LFP. The single spikes and spike bursts fired by the model were locked to a preferred phase of the predominant frequency band where there was a peak in the power of the driving signal. Moreover, the preferred phase of locking shifted with increasing burst size, providing evidence that LFP phase can be encoded by burst size. We also provide initial support for the model results by analysing example data of spontaneous LFP and spiking activity recorded from the subiculum of a single urethane-anaesthetised rat. Subicular neurons fired single spikes, two-spike bursts and larger bursts that locked to a preferred phase of either dominant slow oscillations or theta rhythms within the LFP, according to the model prediction. Both power-modulated phase-locking and gradual shift in the preferred phase of locking as a function of burst size suggest that neurons can use bursts to encode timing information contained in LFP phase into a spike-count code.

Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo.

Mouse Alzheimer's disease (AD) models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct') and long-latency (presumably polysynaptic: 're-entrant') responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice could be due to the development of an abnormal hyper-excitable state in the hippocampal formation.

Episodic-like memory is sensitive to both Alzheimer's-like pathological accumulation and normal ageing processes in mice.

Episodic memory depends on the hippocampus and is sensitive to both Alzheimer's disease (AD) pathology and normal ageing. We showed previously that 3xTgAD mice express a specific, episodic-memory deficit at 6 months of age in the What-Where-Which occasion (WWWhich) task (Davis, Easton, Eacott and Gigg, 2013). This task requires the integration of object-location and contextual cues to form an episodic-like memory. Here, we explore the cumulative effect of AD pathology on WWWhich memory by testing very young and middle-aged mice (3 and 12 months old, respectively). For comparison, we included an alternative episodic-like task (What-Where-When; WWWhen) and an object temporal order (Recency) task to explore claims that WWWhen types of memory are open to non-episodic solutions. We found that in contrast to their performance at 6 months, 3-month-old 3xTgAD mice formed WWWhich episodic-like memories; however, their performance at this age was poorer than in matched controls. In contrast, 3xTgAD and control animals aged 12 months were both impaired on the WWWhich task. Finally, 3xTgAD mice with a WWWhich deficit were unimpaired in both Recency and WWWhen tasks. These results support conclusions that: (1) young 3xTgAD mice express episodic-like memory, albeit depressed relative to controls; (2) age-related changes result in a deficit on the hippocampal-dependent WWWhich episodic memory task; and (3) control and 3xTgAD mice can use recency (trace strength) rather than episodic-like memory for tasks that contain a temporal 'When' component. These results, in combination with our previous findings, support an age-related decline in WWWhich episodic-like memory in mice. Furthermore, this decline is accelerated in the 3xTgAD model.

Episodic-like memory for what-where-which occasion is selectively impaired in the 3xTgAD mouse model of Alzheimer's disease.

Episodic memory loss is a defining feature of early-stage Alzheimer's disease (AD). A test of episodic-like memory for the rat, the What-Where-Which occasion task (WWWhich), requires the association of object, location, and contextual information to form an integrated memory for an event. The WWWhich task cannot be solved by use of non-episodic information such as object familiarity and is dependent on hippocampal integrity. Thus, it provides an ideal tool with which to test capacity for episodic-like memory in the 3xTg murine model for AD. As this model captures much of the human AD phenotype, we hypothesized that these mice would show a deficit in the WWWhich episodic-like memory task. To test the specificity of any episodic-like deficit, we also examined whether mice could perform components of the WWWhich task that do not require episodic-like memory. These included object (Novel Object Recognition), location (Object Location Task, What-Where task), and contextual (What-Which) memory, as well as another three-component task that can be solved without reliance on episodic recall (What-Where-When; WWWhen). The results demonstrate for the first time that control 129sv/c57bl6 mice could form WWWhich episodic-like memories, whereas, 3xTgAD mice at 6 months of age were impaired. Importantly, while 3xTgAD mice showed some deficit on spatial component tasks, they were unimpaired in the more complex WWWhen combination task (which includes a spatial component and is open to non-episodic solutions). These results strongly suggest that AD pathology centered on the hippocampal formation mediates a specific deficit for WWWhich episodic-like memory in the 3xTgAD model.

Effects of increased spatial complexity on behavioural development and task performance in Lister Hooded rats.

Enhancing laboratory animal welfare, particularly in rodents, has been achieved through environmental enrichment in caging systems. Traditional enrichment such as adding objects has shown to impact development, reproductive and maternal performance as well as cognition. However, effects of increased spatial complexity as part of larger novel caging systems have not been investigated. While adoption of caging systems with increased spatial complexity seems uncontroversial from a welfare perspective, effects of such housing on the development and task performance of experimental animals remains unclear. In this study, we investigate differences in key behaviours and cognitive performance between Lister Hooded rats housed in traditional (single-shelf) cages ('basic') and those housed in larger cages with an additional shelf ('enriched'). We found minor differences in maternal behaviour, such as nursing and offspring development. Further, we compared task performance in females, using a hippocampus-dependent task (T-maze) and a hippocampus-independent task (Novel Object Recognition, NOR). While in the T-maze no differences in either the rate of learning or probe trial performance were found, in the NOR task females housed in enriched cages performed better than those housed in basic cages. Our results show that increased spatial complexity does not significantly affect development and maternal performance but may enhance learning in females for a non-spatial task. Increased spatial complexity does not appear to have the same effects on behaviour and development as traditional enrichment. Thus, our results suggest no effect of housing conditions on the development of most behaviours in experimental animals housed in spatially enriched caging systems.

Inverse current source density method in two dimensions: inferring neural activation from multielectrode recordings.

The recent development of large multielectrode recording arrays has made it affordable for an increasing number of laboratories to record from multiple brain regions simultaneously. The development of analytical tools for array data, however, lags behind these technological advances in hardware. In this paper, we present a method based on forward modeling for estimating current source density from electrophysiological signals recorded on a two-dimensional grid using multi-electrode rectangular arrays. This new method, which we call two-dimensional inverse Current Source Density (iCSD 2D), is based upon and extends our previous one- and three-dimensional techniques. We test several variants of our method, both on surrogate data generated from a collection of Gaussian sources, and on model data from a population of layer 5 neocortical pyramidal neurons. We also apply the method to experimental data from the rat subiculum. The main advantages of the proposed method are the explicit specification of its assumptions, the possibility to include system-specific information as it becomes available, the ability to estimate CSD at the grid boundaries, and lower reconstruction errors when compared to the traditional approach. These features make iCSD 2D a substantial improvement over the approaches used so far and a powerful new tool for the analysis of multielectrode array data. We also provide a free GUI-based MATLAB toolbox to analyze and visualize our test data as well as user datasets.

The subiculum comes of age.

The subiculum has long been considered as a simple bidirectional relay region interposed between the hippocampus and the temporal cortex. Recent evidence, however, suggests that this region has specific roles in the cognitive functions and pathological deficits of the hippocampal formation. A group of 20 researchers participated in an ESF-sponsored meeting in Oxford in September, 2005 focusing on the neurobiology of the subiculum. Each brought a distinct expertise and approach to the anatomy, physiology, psychology, and pathologies of the subiculum. Here, we review the recent findings that were presented at the meeting.