Cognition in Meningioma: Effects of Tumor Location and Tumor Removal.

Background: Meningiomas are the most common type of primary intracranial tumor, yet very few studies have assessed the effects of tumor removal.

Methods: Here we report analysis of patients with meningiomas who underwent routine neuropsychological assessment and surgery at a National Health Service (NHS) hospital in the North East of England over a 6-year period.

Results: Surgical removal of tumors significantly improved both phonemic and semantic verbal fluency and some measures of working memory and declarative memory.

Unifying Subicular Function: A Predictive Map Approach.

The successor representation has emerged as a powerful model for understanding mammalian navigation and memory; explaining the spatial coding properties of hippocampal place cells and entorhinal grid cells. However, the diverse spatial responses of subicular neurons, the primary output of the hippocampus, have eluded a unified account. Here, we demonstrate that incorporating rodent behavioural biases into the successor representation successfully reproduces the heterogeneous activity patterns of subicular neurons.

Frequency matters: how changes in hippocampal theta frequency can influence temporal coding, anxiety-reduction, and memory.

Hippocampal theta frequency is a somewhat neglected topic relative to theta power, phase, coherence, and cross-frequency coupling. Accordingly, here we review and present new data on variation in hippocampal theta frequency, focusing on functional associations (temporal coding, anxiety reduction, learning, and memory). Taking the rodent hippocampal theta frequency to running-speed relationship as a model, we identify two doubly-dissociable frequency components: (a) the slope component of the theta frequency-to-stimulus-rate relationship ("theta slope"); and (b) its y-intercept frequency ("theta intercept").

Neural correlates of distinct levels of predatory threat in dorsal periaqueductal grey neurons.

The dorsal periaqueductal grey (PAG) is an important site for integrating predatory threats. However, it remains unclear whether predator-related activation in PAG primarily reflects threat itself and thus can distinguish between various degrees of threat, or rather reflects threat-oriented behaviours, with the PAG potentially orchestrating different types of defensive repertoire. To address this issue, we performed extracellular recording of dorsal PAG neurons in freely behaving rats and examined neuronal and behavioural responses to stimulus conditions with distinct levels of predatory threat.

Vector trace cells in the subiculum of the hippocampal formation.

Successfully navigating in physical or semantic space requires a neural representation of allocentric (map-based) vectors to boundaries, objects and goals. Cognitive processes such as path-planning and imagination entail the recall of vector representations, but evidence of neuron-level memory for allocentric vectors has been lacking. Here, we describe a novel neuron type, vector trace cell (VTC), whose firing generates a new vector field when a cue is encountered and a 'trace' version of that field for hours after cue removal.

Acetylcholine and Spontaneous Recognition Memory in Rodents and Primates.

Whilst acetylcholine has long been linked to memory, there have been significant questions about its specific role. In particular, the effects of cholinergic manipulations in primates and rodents has often been at odds. Here, we review the work in primates and rodents on the specific function of acetylcholine in memory, and episodic memory in particular.

Distinct and combined responses to environmental geometry and features in a working-memory reorientation task in rats and chicks.

The original provocative formulation of the 'geometric module' hypothesis was based on a working-memory task in rats which suggested that spontaneous reorientation behavior is based solely on the environmental geometry and is impervious to featural cues. Here, we retested that claim by returning to a spontaneous navigation task with rats and domestic chicks, using a single prominent featural cue (a striped wall) within a rectangular arena. Experiments 1 and 2 tested the influence of geometry and features separately.

Insoluble Aβ overexpression in an knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, affecting anxiety-related behaviours.

We studied a new amyloid-beta precursor protein () knock-in mouse model of Alzheimer's disease ( ), containing the Swedish KM670/671NL mutation, the Iberian I716F mutation and the Artic E693G mutation, which generates elevated levels of amyloid beta (Aβ) and Aβ without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. knock-in mice exhibited subtle deficits in tasks assessing social olfaction, but not in social motivation tasks.

En route to delineating hippocampal roles in spatial learning.

The precise role played by the hippocampus in spatial learning tasks, such as the Morris Water Maze (MWM), is not fully understood. One theory is that the hippocampus is not required for 'knowing where' but rather is crucial in 'getting there'. To explore this idea in the MWM, we manipulated 'getting there' variables, such as passive transport or active swimming towards the hidden platform, in rats with and without hippocampal lesions.

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in deletion mice.

Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored.

The Neurobiology of Mammalian Navigation.

Mammals have evolved specialized brain systems to support efficient navigation within diverse habitats and over varied distances, but while navigational strategies and sensory mechanisms vary across species, core spatial components appear to be widely shared. This review presents common elements found in mammalian spatial mapping systems, focusing on the cells in the hippocampal formation representing orientational and locational spatial information, and 'core' mammalian hippocampal circuitry. Mammalian spatial mapping systems make use of both allothetic cues (space-defining cues in the external environment) and idiothetic cues (cues derived from self-motion).

Hippocampal CA1 activity correlated with the distance to the goal and navigation performance.

Coding the distance to a future goal is an important function of a neural system supporting navigation. While some evidence indicates the hippocampus increases activity with proximity to the goal, others have found activity to decrease with proximity. To explore goal distance coding in the hippocampus we recorded from CA1 hippocampal place cells in rats as they navigated to learned goals in an event arena with a win-stay lose-shift rule.

Reconciling the different faces of hippocampal theta: The role of theta oscillations in cognitive, emotional and innate behaviors.

The theta oscillation (5-10Hz) is a prominent behavior-specific brain rhythm. This review summarizes studies showing the multifaceted role of theta rhythm in cognitive functions, including spatial coding, time coding and memory, exploratory locomotion and anxiety-related behaviors. We describe how activity of hippocampal theta rhythm generators - medial septum, nucleus incertus and entorhinal cortex, links theta with specific behaviors.

Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.

The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer's disease (AD), and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment (MCI) due to AD.

Heterozygous deletion of α-neurexin I or α-neurexin II results in behaviors relevant to autism and schizophrenia.

The neurexins are a family of presynaptic cell adhesion molecules. Human genetic studies have found heterozygous deletions affecting NRXN1 and NRXN2, encoding α-neurexin I (Nrxn1α) and α-neurexin II (Nrxn2α), in individuals with autism spectrum disorders and schizophrenia. However, the link between α-neurexin deficiency and the manifestation of psychiatric disorders remain unclear.

Know your limits: the role of boundaries in the development of spatial representation.

In this issue of Neuron,Bjerknes et al. (2014) show that cells responding to environmental boundaries (border/boundary cells) are present as soon as rat pups can independently explore their environment. These boundary-based representations may thus provide a scaffold for other, later emerging, spatial representations.

The Behavioural Inhibition System, anxiety and hippocampal volume in a non-clinical population.

Background: Animal studies have suggested that the hippocampus may play an important role in anxiety as part of the Behavioural Inhibition System (BIS), which mediates reactivity to threat and punishment and can predict an individual's response to anxiety-relevant cues in a given environment. The aim of the present structural magnetic resonance imaging (MRI) study was to examine the relationship between individual differences in BIS and hippocampal structure, since this has not received sufficient attention in non-clinical populations. Thirty healthy right-handed participants with no history of alcohol or drug abuse, neurological or psychiatric disorders, or traumatic brain injury were recruited (16 male, 14 female, age 18 to 32 years).

Anxiolytic drugs and altered hippocampal theta rhythms: the quantitative systems pharmacological approach.

The spirit of systems pharmacology was adopted to study the possible mechanisms of anxiolytic drugs on hippocampal electric patterns. The frequency of the hippocampal theta rhythm increases linearly with the intensity of electrical stimulation to the brainstem. The reduction of mean theta frequency in this paradigm predicts the clinical efficacy of anxiolytic drugs.

How environment geometry affects grid cell symmetry and what we can learn from it.

The mammalian hippocampal formation provides neuronal representations of environmental location but the underlying mechanisms are unclear. The majority of cells in medial entorhinal cortex and parasubiculum show spatially periodic firing patterns. Grid cells exhibit hexagonal symmetry and form an important subset of this more general class.

Boundary coding in the rat subiculum.

The spatial mapping function of the hippocampal formation is likely derived from two sets of information: one based on the external environment and the other based on self-motion. Here, we further characterize 'boundary vector cells' (BVCs) in the rat subiculum, which code space relative to one type of cue in the external environment: boundaries. We find that the majority of cells with fields near the perimeter of a walled environment exhibit an additional firing field when an upright barrier is inserted into the walled environment in a manner predicted by the BVC model.

Space in the brain: how the hippocampal formation supports spatial cognition.

Over the past four decades, research has revealed that cells in the hippocampal formation provide an exquisitely detailed representation of an animal's current location and heading. These findings have provided the foundations for a growing understanding of the mechanisms of spatial cognition in mammals, including humans. We describe the key properties of the major categories of spatial cells: place cells, head direction cells, grid cells and boundary cells, each of which has a characteristic firing pattern that encodes spatial parameters relating to the animal's current position and orientation.

Evidence for encoding versus retrieval scheduling in the hippocampus by theta phase and acetylcholine.

The formation of new memories requires new information to be encoded in the face of proactive interference from the past. Two solutions have been proposed for hippocampal region CA1: (1) acetylcholine, released in novelty, selectively suppresses excitatory projections to CA1 from CA3 (mediating the products of retrieval), while sparing entorhinal inputs (mediating novel sensory information) and (2) encoding preferentially occurs at the pyramidal-layer theta peak, coincident with input from entorhinal cortex, and retrieval occurs at the trough, coincident with input from CA3, consistent with theta phase-dependent synaptic plasticity. We examined three predictions of these models: (1) in novel environments, the preferred theta phase of CA1 place cell firing should shift closer to the CA1 pyramidal-layer theta peak, shifting the encoding-retrieval balance toward encoding; (2) the encoding-related shift in novel environments should be disrupted by cholinergic antagonism; and (3) in familiar environments, cholinergic antagonism should shift the preferred theta firing phase closer to the theta trough, shifting the encoding-retrieval balance even further toward retrieval.

Novelty and anxiolytic drugs dissociate two components of hippocampal theta in behaving rats.

Hippocampal processing is strongly implicated in both spatial cognition and anxiety and is temporally organized by the theta rhythm. However, there has been little attempt to understand how each type of processing relates to the other in behaving animals, despite their common substrate. In freely moving rats, there is a broadly linear relationship between hippocampal theta frequency and running speed over the normal range of speeds used during foraging.

A specific role for septohippocampal acetylcholine in memory?

Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the specific role for this neurotransmitter is difficult to identify in human neuropsychology. Here, we review the evidence for a mechanistic model of acetylcholine function within the hippocampus and consider its explanatory power for interpreting effects resulting from both pharmacological anticholinergic manipulations and lesions of the cholinergic input to the hippocampus in animals. We argue that these effects indicate that acetylcholine is necessary for some, but not all, hippocampal-dependent processes.

The virtues of youth and maturity (in dentate granule cells).

How does adult neurogenesis contribute to memory? Nakashiba and colleagues generated mutant mice in which synaptic output from older hippocampal granule cells was specifically blocked. Experiments with these mice reveal an unpredicted age-dependent specialization of function, demonstrating that recently born cells support pattern separation, whereas older cells support pattern completion.