Brain and neuroscience advances最新文献

We examined the role of the hippocampus and the dorsolateral striatum in the representation of environmental geometry using a spontaneous object recognition procedure. Rats were placed in a kite-shaped arena and allowed to explore two distinctive objects in each of the right-angled corners. In a different room, rats were then placed into a rectangular arena with two identical copies of one of the two objects from the exploration phase, one in each of the two adjacent right-angled corners that were separated by a long wall. Time spent exploring these two objects was recorded as a measure of recognition memory. Since both objects were in different locations with respect to the room (different between exploration and test phases) and the global geometry (also different between exploration and test phases), differential exploration of the objects must be a result of initial habituation to the object relative to its local geometric context. The results indicated an impairment in processing the local geometric features of the environment for both hippocampus and dorsolateral striatum lesioned rats compared with sham-operated controls, though a control experiment showed these rats were unimpaired in a standard object recognition task. The dorsolateral striatum has previously been implicated in egocentric route-learning, but the results indicate an unexpected role for the dorsolateral striatum in processing the spatial layout of the environment. The results provide the first evidence that lesions to the hippocampus and dorsolateral striatum impair spontaneous encoding of local environmental geometric features.

Insulin sensitivity, pancreatic β-cell function, fasting glucose, and 2-h post-load glucose were related to cognition in cognitively healthy nondiabetic older adults. Thirty-five adults (⩾65 years) underwent a 2-h oral glucose tolerance test and cognitive testing. Seventeen had normal glucose tolerance and 18 had intermediate hyperglycaemia or prediabetes (World Health Organization criteria). Fasting glucose and 2-h post-load glucose and oral glucose tolerance test-derived measures of β-cell function (oral disposition index) and insulin sensitivity were analysed as predictors of four cognitive domains: verbal episodic memory, verbal fluency, executive function, and working memory. The prediabetes group had significantly worse working memory performance than the normal glucose tolerance group. Controlling for age and education, decreased oral disposition index, and increased 2-h post-load glucose were significantly related to worse working memory performance. Prediabetes may worsen working memory in healthy older adults. Reduced pancreatic β-cell function should be investigated as a contributor to age-related cognitive decline.

Polymorphisms in the apolipoprotein E (APOE) gene have been associated with individual differences in cognition, brain structure and brain function. For example, the ε4 allele has been associated with cognitive and brain impairment in old age and increased risk of dementia, while the ε2 allele has been claimed to be neuroprotective. According to the 'antagonistic pleiotropy' hypothesis, these polymorphisms have different effects across the lifespan, with ε4, for example, postulated to confer benefits on cognitive and brain functions earlier in life. In this stage 2 of the Registered Report - https://osf.io/bufc4, we report the results from the cognitive and brain measures in the Cambridge Centre for Ageing and Neuroscience cohort (www.cam-can.org). We investigated the antagonistic pleiotropy hypothesis by testing for allele-by-age interactions in approximately 600 people across the adult lifespan (18-88 years), on six outcome variables related to cognition, brain structure and brain function (namely, fluid intelligence, verbal memory, hippocampal grey-matter volume, mean diffusion within white matter and resting-state connectivity measured by both functional magnetic resonance imaging and magnetoencephalography). We found no evidence to support the antagonistic pleiotropy hypothesis. Indeed, Bayes factors supported the null hypothesis in all cases, except for the (linear) interaction between age and possession of the ε4 allele on fluid intelligence, for which the evidence for faster decline in older ages was ambiguous. Overall, these pre-registered analyses question the antagonistic pleiotropy of APOE polymorphisms, at least in healthy adults.

The entorhinal-hippocampus network plays a central role in navigation and episodic memory formation. To investigate these interactions, we examined the effect of medial entorhinal cortex lesions on hippocampal place cell activity. Since the medial entorhinal cortex is suggested to play a role in the processing of self-motion information, we hypothesised that such processing would be necessary for maintaining stable place fields in the absence of environmental cues. Place cells were recorded as medial entorhinal cortex-lesioned rats explored a circular arena during five 16-min sessions comprising a baseline session with all sensory inputs available followed by four sessions during which environmental (i.e. visual, olfactory, tactile) cues were progressively reduced to the point that animals could rely exclusively on self-motion cues to maintain stable place fields. We found that place field stability and a number of place cell firing properties were affected by medial entorhinal cortex lesions in the baseline session. When rats were forced to rely exclusively on self-motion cues, within-session place field stability was dramatically decreased in medial entorhinal cortex rats relative to SHAM rats. These results support a major role of the medial entorhinal cortex in processing self-motion cues, with this information being conveyed to the hippocampus to help anchor and maintain a stable spatial representation during movement.

The ketamine metabolite (2R,6R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of (R,S)-ketamine with the (2S,6S)- and (2R,6R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor-dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1-10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2S,6S)-hydroxynorketamine. At a concentration of 10 μM, (2R,6R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor-mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.

Exposure to adverse experiences during development increases the risk of psychiatric illness later in life. Growing evidence suggests a role for the neuroimmune system in this relationship. There is now substantial evidence that the immune system is critical for normal brain development and behaviour, and responds to environmental perturbations experienced early in life. Severe or chronic stress results in dysregulated neuroimmune function, concomitant with abnormal brain morphology and function. Positive experiences including environmental enrichment and exercise exert the opposite effect, promoting normal brain and immune function even in the face of early life stress. The neuroimmune system may therefore provide a viable target for prevention and treatment of psychiatric illness. This review will briefly summarise the neuroimmune system in brain development and function, and review the effects of stress and positive environmental experiences during development on neuroimmune function. There are also significant sex differences in how the neuroimmune system responds to environmental experiences early in life, which we will briefly review.

For the first time, we assess episodic simulation in a patient with visual memory deficit amnesia, following damage to visual association cortices. Compared to control participants, the patient with visual memory deficit amnesia shows severely restricted responses when asked to simulate different types of future episodic scenarios. Surprisingly, the patient's responses are more limited in cases where the scenarios require less reliance on visual information. We explain this counterintuitive finding through discussing how the severe retrograde amnesia in visual memory deficit amnesia limits the patient's access to episodic memories in which vision has not been a focus of their life. As a result, we argue that the deficits in visual memory deficit amnesia continue to distinguish it from amnesia after direct damage to the hippocampus.

Despite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle. The mouse data were collated from the Allen Mouse Brain Atlas. The projections from the three major anterior thalamic nuclei occupied much of the external medullary stratum of the cingulum bundle, where they were concentrated in its more medial portions. These anterior thalamic projections formed a rostral-reaching basket of efferents prior to joining the cingulum bundle, with anteromedial efferents taking the most rostral routes, often reaching the genu of the corpus callosum, while anterodorsal efferents took the least rostral route. In contrast, the return cortico-anterior thalamic projections frequently crossed directly through the bundle or briefly joined the internal stratum of the cingulum bundle, often entering the internal capsule before reaching the anterior thalamus. These analyses confirm that anterior thalamic connections comprise an important component of the rodent cingulum bundle, while also demonstrating the very different routes used by thalamo-cortical and cortico-thalamic projections. This information reveals how the composition of the cingulum bundle alters along its length.

In humans, most of our new memories are in some way or another related to what we have already experienced. However, in memory research, especially in non-human animal research, subjects are often mostly naïve to the world. But we know that previous knowledge will change how memories are processed and which brain areas are critical at which time point. Each process from encoding, consolidation, to memory retrieval will be affected. Here, we summarise previous knowledge effects on the neurobiology of memory in both humans and non-human animals, with a special focus on schemas - associative network structures. Furthermore, we propose a new theory on how there may be a continuous gradient from naïve to expert, which would modulate the importance and role of brain areas, such as the hippocampus and prefrontal cortex.

Systemic inflammation has been associated with negative mood states and human sickness behaviour. Previous studies have shown an association between systemic inflammation and changes in task-related blood-oxygen-level-dependent activity and functional connectivity within large-scale networks. However, no study has examined the effect of inflammation on the magnitude of blood-oxygen-level-dependent low-frequency fluctuations at rest. We used a double-blind placebo-controlled crossover design to randomise 20 male subjects (aged 20-50 years) to receive either a Salmonella typhi vaccine or a placebo saline injection at two separate sessions. All participants underwent a resting-state functional magnetic resonance scan and a measure of inflammation (interleukin 6) and mood (Profile of Mood States) 3 h after injection. We compared the whole brain amplitude of low-frequency fluctuations between the vaccine and placebo conditions using a repeated measures design. Vaccine condition was associated with greater interleukin 6 levels (p < 0.001). Vaccine condition was also associated with lower amplitude of low-frequency fluctuations in the right and left frontal pole, superior frontal gyrus, paracingulate gyrus (Cluster 1) and the right mid and inferior frontal gyrus (Cluster 2) (p < 0.001, false discovery rate corrected). Lower amplitude of low-frequency fluctuations pertaining to first cluster correlated with greater total Profile of Mood States score (worse mood) (r = -0.38; p = 0.04). These results imply possible excitation/inhibition imbalance mechanisms during inflammation that may be a relevant target in psychiatric disease, especially mood disorders.