Neuroscience
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The hippocampal CA1 region receives cortical information via two main inputs: directly via the perforant (temporoammonic) path (pp-CA1 synapse) and indirectly via the tri-synaptic pathway. Although synaptic plasticity has been reported at the pp-CA1 synapse of freely behaving animals, the mechanisms underlying this phenomenon have not been investigated. Here, we explored whether long-term potentiation (LTP) at the pp-CA1 synapse in freely behaving rats requires activation of N-methyl-d-aspartate receptors (NMDAR) and L-type voltage-gated calcium channels (VGCCs). ⋯ Whereas activation of group II mGlu receptors using (1R,2R)-3-((1S)-1-amino-2-hydroxy-2-oxoethyl) cyclopropane-1,2-dicarboxylic acid (DCG-IV) dose-dependently reduced basal synaptic transmission elicited by test-pulse stimulation, DCG-IV did not affect LTP in a dose that inhibited LTP at pp-DG synapses in vivo. These data indicate that LTP at the pp-CA1 synapse of freely behaving animals is dually dependent on NMDAR and VGCCs, whereby group II mGlu receptor activation affect basal synaptic tonus, but not LTP. The lower frequency-dependency of NMDA-VGCC LTP at pp-CA1 synapses compared to pp-DG synapses may comprise a mechanism to prioritize information processing at this synapse.
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Hippocampal circuits are among the best described networks in the mammalian brain, particularly with regard to the alterations that arise during normal aging. Decades of research indicate multiple points of vulnerability in aging neural circuits, and it has been proposed that each of these changes make a contribution to observed age-related cognitive deficits. Another view has been relatively overlooked - namely that some of these changes arise in adaptive response to protect network function in aged animals. ⋯ Using the hippocampus as a model neural circuit we discuss how, in normally aged animals, some age-related changes may arise through processes of neural plasticity that serve to enhance network function rather than to hinder it. Conceptually disentangling the initial age-related vulnerabilities from changes that result in adaptive response will be a major challenge for the future research on brain aging. We suggest that a reformulation of how normal aging could be understood from an adaptive perspective will lead to a deeper understanding of the secrets behind successful brain aging and our recent cultural successes in facilitating these processes.
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One of the most replicated findings has been that hippocampus volume is decreased in patients with major depressive disorder (MDD). Recent volumetric magnetic resonance imaging (MRI) studies suggest that localized differences in hippocampal volume may be more prominent than global differences. ⋯ The results of these studies provide the first in vivo evidence that hippocampal volume reductions in MDD are specific to the cornu ammonis and dentate gyrus hippocampal subfields, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. In this review we discuss how recent advances in neuroimaging allow researchers to further understand hippocampal neuroplasticity in MDD and how it is related to antidepressant treatment, memory function, and disease progression.
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Transient global ischemia selectively damages neurons in specific brain areas. A reproducible pattern of selective vulnerability is observed in the dorsal hippocampus of rodents where ischemic damage typically affects neurons in the CA1 area while sparing neurons in CA3 and granule cells. The "neuronal factors" underlying the differential vulnerability of CA1 versus CA3 have been of great interest. ⋯ A survey of selective vulnerability in the human hippocampus in relation to genomic studies in ischemia-hypoxia is presented, and neurodegeneration genes with high expression in CA1 are highlighted (e.g. WFS1). It is concluded that neuronal factors dominate the selective vulnerability of CA1 but that vascular factors also deserve more systematic studies.
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A consequence of normal aging is a greater susceptibility to memory impairments following an immune challenge such as infection, surgery, or traumatic brain injury. The neuroinflammatory response, produced by these challenges results in increased and prolonged production of pro-inflammatory cytokines in the otherwise healthy aged brain. ⋯ We review the current understanding of the causes and effects of normal aging-induced microglial sensitization, including dysregulations of the neuroendocrine system, potentiation of neuroinflammatory responses following an immune challenge, and the impairment of memories. We end with a discussion of therapeutic approaches to prevent these deleterious effects.