Imaging of C-fos Activity in Neurons of the Mouse Parietal Association Cortex during Acquisition and Retrieval of Associative Fear Memory

The parietal cortex of rodents participates in sensory and spatial processing, movement planning, and decision-making, but much less is known about its role in associative learning and memory formation. The present study aims to examine the involvement of the parietal association cortex (PtA) in associative fear memory acquisition and retrieval in mice. Using ex vivo c-Fos immunohistochemical mapping and in vivo Fos-EGFP two-photon imaging, we show that PtA neurons were specifically activated both during acquisition and retrieval of cued fear memory. Fos immunohistochemistry revealed specific activation of the PtA neurons during retrieval of the 1-day-old fear memory. In vivo two-photon Fos-EGFP imaging confirmed this result and in addition detected specific c-Fos responses of the PtA neurons during acquisition of cued fear memory. To allow a more detailed study of the long-term activity of such PtA engram neurons, we generated a Fos-Cre-GCaMP transgenic mouse line that employs the Targeted Recombination in Active Populations (TRAP) technique to detect calcium events specifically in cells that were Fos-active during conditioning. We show that gradual accumulation of GCaMP3 in the PtA neurons of Fos-Cre-GCaMP mice peaks at the 4th day after fear learning. We also describe calcium transients in the cell bodies and dendrites of the TRAPed neurons. This provides a proof-of-principle for TRAP-based calcium imaging of PtA functions during memory processes as well as in experimental models of fear- and anxiety-related psychiatric disorders and their specific therapies.

Inactivation of Prefrontal Cortex Delays Emergence From Sevoflurane Anesthesia

Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex—somatosensory barrel field and medial/lateral parietal association cortex—would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.

Human Prefrontal Cortex

This chapter and the next one consider how to account for the astonishing difference in intelligence between humans and our nearest living ancestors, the great apes. An integrated system that includes the dorsal prefrontal cortex and the parietal association cortex is activated when subjects attempt tests of non-verbal intelligence. It has been suggested that this system might act as a ‘multiple-demand system’ or ‘global workspace’ that can deal with any problem. However, closer examination suggests that the tasks used to support this claim have in common that they involve abstract sequences. These problems can be solved by visual imagery alone. But humans also have the advantage that they also have access to a propositional code. This means that they can solve problems that involve verbal reasoning, as well as being able to form detailed plans for the future. They can also form explicit judgements about themselves, including their perceptions, actions, and memories, and this means that they can represent themselves as individuals. The representation of the self depends in part on tissue in the medial prefrontal cortex (PF).

Multiplexed fractionated proteomics reveals synaptic factors associated with cognitive resilience in Alzheimer's Disease

Alzheimer's disease (AD) is a complex neurodegenerative disease defined by the presence of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles, and driven by dysproteostatis, inflammation, metabolic dysfunction, and oxidative injury, eventually leading to synapse loss and cell death. Synapse loss correlates with cognitive impairment and may occur independently of the extent of AD pathology. To understand how synaptic composition is changed in relation to AD neuropathology and cognition, highly sensitive multiplexed liquid chromatography mass-spectrometry was used to quantify biochemically enriched synaptic proteins from the parietal association cortex of 100 subjects with contrasting AD pathology and cognitive performance. Functional analysis showed preservation of synaptic signaling, ion transport, and mitochondrial proteins in normal aged and "resilient" (cognitively unimpaired with AD pathology) individuals. Compared to these individuals, those with cognitive impairment showed significant metabolic differences and increased immune- and inflammatory-related proteins, establishing the synapse as a potential integration point for multiple AD pathophysiologies.

Macroscale Cortical Organization and a Default-Like Transmodal Apex Network in the Marmoset Monkey

Networks of widely distributed regions populate human association cortex. One network, often called the default network, is positioned at the apex of a gradient of sequential networks that radiate outward from primary cortex. Here extensive anatomical data made available through the Marmoset Brain Architecture Project were explored to determine if a homologue exists in marmoset. Results revealed that a gradient of networks extend outward from primary cortex to progressively higher-order transmodal association cortex in both frontal and temporal cortex. The transmodal apex network comprises frontopolar and rostral temporal association cortex, parahippocampal areas TH / TF, the ventral posterior midline, and lateral parietal association cortex. The positioning of this network in the gradient and its composition of areas make it a candidate homologue to the human default network. That the marmoset, a physiologically- and genetically-accessible primate, might possess a default-network-like candidate creates opportunities for study of higher cognitive and social functions.

Evolution of cognitive and neural solutions enabling numerosity judgements: lessons from primates and corvids

Brains that are capable of representing numerosity, the number of items in a set, have arisen repeatedly and independently in different animal taxa. This review compares the cognitive and physiological mechanisms found in a nonhuman primate, the rhesus macaque, and a corvid songbird, the carrion crow, in order to elucidate the evolutionary adaptations underlying numerical competence. Monkeys and corvids are known for their advanced cognitive competence, despite them both having independently and distinctly evolved endbrains that resulted from a long history of parallel evolution. In both species, numerosity is represented as an analogue magnitude by an approximate number system that obeys the Weber–Fechner Law. In addition, the activity of numerosity-selective neurons in the fronto-parietal association cortex of monkeys and the telencephalic associative area nidopallium caudolaterale of crows mirrors the animals' performance. In both species' brains, neuronal activity is tuned to a preferred numerosity, encodes the numerical value in an approximate fashion, and is best represented on a logarithmic scale. Collectively, the data show an impressive correspondence of the cognitive and neuronal mechanisms for numerosity representations across monkeys and crows. This suggests that remotely related vertebrates with distinctly developed endbrains adopted similar physiological solutions to common computational problems in numerosity processing. This article is part of a discussion meeting issue ‘The origins of numerical abilities'.

Effects of intracranial meningioma location, size, and surgery on neurocognitive functions: a 3-year prospective study

OBJECT Current recommendations stress the need for cognitive parameters to be integrated in the evaluation of outcomes for intracranial meningioma surgery. The aim of this prospective study was to examine neurocognitive function in meningioma patients pre- and postoperatively. METHODS Patients with skull base (anterior and middle fossa) and convexity (anterior and posterior) meningiomas (n = 54) underwent neuropsychological examination prior to and 1 year after surgery. A control group (n = 52) of healthy volunteers matched for age, sex, and education underwent the same examination. Assessments included executive, memory, and motor functions with standardized testing. Patients with convexity meningiomas were clinically assessed for parietal association cortex functions. RESULTS All patients performed significantly worse (p < 0.05) in most neurocognitive domains than controls. The skull base group showed more disturbances in memory than the convexity group (p < 0.05). The anterior convexity group showed more deficits in executive function than the posterior convexity group, which presented with parietal association cortex deficits. Verbal deficits were more pronounced in the left hemisphere than in the right hemisphere. Patients with a large tumor (> 4 cm) had more severe neurocognitive deficits than those with a small tumor (< 4 cm). Postoperatively, patients showed no deterioration in neurocognitive function. Instead, significant improvement (p < 0.05) was observed in some executive, motor, and parietal association cortex functions. CONCLUSIONS According to the authors’ findings, intracranial meningiomas may cause neurocognitive deficits in patients. Surgery does not cause a deterioration in cognitive function; instead, it may lead to improvements in some functions. Permanent neuropsychological postoperative deficits should be interpreted as tumor-induced rather than due to surgery.