Homeostatic plasticity maintains network stability by adjusting excitation, inhibition, or the intrinsic excitability of neurons, but the developmental regulation and coordination of these distinct forms of homeostatic plasticity remains poorly understood. A major contributor to this information gap is the lack of a uniform paradigm for chronically manipulating activity at different developmental stages. To overcome this limitation, we used designer receptors exclusively activated by designer drugs (DREADDs) to directly suppress neuronal activity in layer2/3 (L2/3) of mouse primary visual cortex of either sex at two important developmental timepoints: the classic visual system critical period [CP; postnatal day 24 (P24) to P29], and adulthood (P45 to P55). We show that 24 h of DREADD-mediated activity suppression simultaneously induces excitatory synaptic scaling up and intrinsic homeostatic plasticity in L2/3 pyramidal neurons during the CP, consistent with previous observations using prolonged visual deprivation. Importantly, manipulations known to block these forms of homeostatic plasticity when induced pharmacologically or via visual deprivation also prevented DREADD-induced homeostatic plasticity. We next used the same paradigm to suppress activity in adult animals. Surprisingly, while excitatory synaptic scaling persisted into adulthood, intrinsic homeostatic plasticity was completely absent. Finally, we found that homeostatic changes in quantal inhibitory input onto L2/3 pyramidal neurons were absent during the CP but were present in adults. Thus, the same population of neurons can express distinct sets of homeostatic plasticity mechanisms at different development stages. Our findings suggest that homeostatic forms of plasticity can be recruited in a modular manner according to the evolving needs of a developing neural circuit.
Functional neuroimaging studies have implicated the hippocampus formation in the pathophysiology of bipolar disorder, but findings from volumetric studies have been less consistent. The authors aim to further investigate the existence of volumetric abnormalities in the hippocampus of individuals with bipolar disorder. In addition to methodological inconsistencies, many previous studies have been lacking clinical robustness with respect to characterizing bipolar patients and comparison subjects. Hence, the present study matched the groups closely across a number of demographic parameters. Using MRI, hippocampal volumes of 24 bipolar patients were compared to 24 sex-, age-, and education-matched comparison subjects, and these findings were further investigated in relation to both illness and treatment factors. A significantly larger (8.5%) right hippocampus was seen in bipolar patients than in comparison subjects, and this difference was not associated with a history of psychosis, familial illness, or lithium treatment, after controlling for potential confounds. Patients reporting fewer affective episodes did however have significantly larger left hippocampus volumes than comparison subjects. The authors found that the left hippocampus was larger in a group of adult bipolar subjects relative to the healthy comparison group. The reason for this is unclear, but in this sample, it was not associated with family history, psychotic features, or medication exposure. A negative association was found between left hippocampal volume and number of episodes or duration of illness, suggesting the hippocampus might be larger in the early phase of bipolar disorder but becomes smaller with time.
Purpose of review This review discusses recent developments in the application of magnetic particle imaging (MPI) to dementia research. Recent findings MPI is a tracer method that is currently in the preclinical development stage. It provides high sensitivity for the detection and localization of magnetic nanoparticles with very high spatial and temporal resolution and a similar application spectrum as PET. Unlike MRI, the MPI signal is not contaminated by background signal from tissues and is highly quantifiable in terms of local tracer concentrations. These properties make the technology ideally suited for localization of specific targets or quantification of vascular parameters. MPI uses magnetic nanoparticles which can be modified by various coatings, and by adding ligands (i.e. peptides or antibodies) for specific targeting. This makes MPI an attractive tool for the potential detection of abnormal protein deposits, such as Aβ plaques, with greater specificity than MRI. Neural stem cells can also be labelled with these nanoparticles ex vivo to monitor their migration in vivo. Summary The capabilities of MPI opens the potential for several applications of MPI in neurocognitive disorders, including vascular imaging, detection of amyloid plaques and potentially other pathological hallmarks of Alzheimer's disease and stem-cell tracking.
In this research, we investigated the alterations in the directionality and strength of regional interactions within functionally changed brain networks and their relationship to cognitive decline during the aging process in normal elderly individuals. Thirty-seven cognitively normal elderly people received resting-state fMRI scans and cognitive assessments at baseline (age = 78.65 ± 3.56 years) and at 4-year follow-up. Functional connectivity analyses were used to identify networks containing brain regions whose functions changed with age as regions of interest. The spectral dynamic causal modeling (spDCM) method was used to estimate the causal interactions within networks in subjects at different time points and in subjects with different cognitive levels to explore the alterations with cognitive aging. The results showed that, at both time points, all the networks, except the frontal-parietal network (FPN) at baseline, had mutual interactions between each pair of nodes. Furthermore, when the subjects were divided with global cognition level, lost connections were only found in the subgroup with better performance. These indicated that elderly people appeared to need more interaction pathways between brain areas with cognitive decline. We also observed that the strength of the flow of information from the left angular gyrus to the precuneus, which is associated with activation of memory retrieval and the functional hub involved in various cognitive domains, was predictive of declines in executive function with the aging process, making it a potential predictor of such situation.
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