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Hippocampal hub neurons maintain distinct connectivity throughout their lifetime.

ABSTRACT: The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as 'hubs' by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.

SUBMITTER: Bocchio M

PROVIDER: S-EPMC7486410 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Hippocampal hub neurons maintain distinct connectivity throughout their lifetime.

Bocchio Marco M Gouny Claire C Angulo-Garcia David D Toulat Tom T Tressard Thomas T Quiroli Eleonora E Baude Agnès A Cossart Rosa R

Nature communications 20200911 1

The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as 'hubs' by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only o ...[more]

PMID: 32917906

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Project description:During immature stages, adult-born neurons pass through critical periods for survival and plasticity. It is generally assumed that by 2 months of age adult-born neurons are mature and equivalent to the broader neuronal population, raising questions of how they might contribute to hippocampal function in old age when neurogenesis has declined. However, few have examined adult-born neurons beyond the critical period or directly compared them to neurons born in infancy. Here, we used a retrovirus to visualize functionally relevant morphological features of 2- to 24-week-old adult-born neurons in male rats. From 2 to 7 weeks, neurons grew and attained a relatively mature phenotype. However, several features of 7-week-old neurons suggested a later wave of growth: these neurons had larger nuclei, thicker dendrites, and more dendritic filopodia than all other groups. Indeed, between 7 and 24 weeks, adult-born neurons gained additional dendritic branches, formed a second primary dendrite, acquired more mushroom spines, and had enlarged mossy fiber presynaptic terminals. Compared with neonatal-born neurons, old adult-born neurons had greater spine density, larger presynaptic terminals, and more putative efferent filopodial contacts onto inhibitory neurons. By integrating rates of cell birth and growth across the life span, we estimate that adult neurogenesis ultimately produces half of the cells and the majority of spines in the dentate gyrus. Critically, protracted development contributes to the plasticity of the hippocampus through to the end of life, even after cell production declines. Persistent differences from neonatal-born neurons may additionally endow adult-born neurons with unique functions even after they have matured.SIGNIFICANCE STATEMENT Neurogenesis occurs in the hippocampus throughout adult life and contributes to memory and emotion. It is generally assumed that new neurons have the greatest impact on behavior when they are immature and plastic. However, since neurogenesis declines dramatically with age, it is unclear how they might contribute to behavior later in life when cell proliferation has slowed. Here we find that newborn neurons mature over many months in rats and may end up with distinct morphological features compared with neurons born in infancy. Using a mathematical model, we estimate that a large fraction of neurons is added in adulthood. Moreover, their extended growth produces a reserve of plasticity that persists even after neurogenesis has declined to low rates.

Project description:Many of nature’s fractal objects benefit from the favorable functionality that results from their pattern repetition at multiple scales. Our recent research focused on the importance of fractal scaling in establishing connectivity between neurons. Fractal dimension DA of the neuron arbors was shown to relate to the optimization of competing functional constraints—the ability of dendrites to connect to other neurons versus the costs associated with building the dendrites. Here, we consider whether pathological states of neurons might affect this fractal optimization and if changes in DA might therefore be used as a diagnostic tool in parallel with traditional measures like Sholl analyses. We use confocal microscopy to obtain images of CA1 pyramidal neurons in the coronal plane of the dorsal rat hippocampus and construct 3-dimensional models of the dendritic arbors using Neurolucida software. We examine six rodent groups which vary in brain condition (whether they had lesions in the anterior thalamic nuclei, ATN) and experience (their housing environment and experience in a spatial task). Previously, we showed ATN lesions reduced spine density in hippocampal CA1 neurons, whereas enriched housing increased spine density in both ATN lesion and sham rats. Here, we investigate whether ATN lesions and experience also effect the complexity and connectivity of CA1 dendritic arbors. We show that sham rats exposed to enriched housing and spatial memory training exhibited higher complexity (as measured by DA) and connectivity compared to other groups. When we categorize the rodent groups into those with or without lesions, we find that both categories achieve an optimal balance of connectivity with respect to material cost. However, the DA value used to achieve this optimization does not change between these two categories, suggesting any morphological differences induced by the lesions are too small to influence the optimization process. Accordingly, we highlight considerations associated with applying our technique to publicly accessible repositories of neuron images with a broader range of pathological conditions.

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Hippocampal hub neurons maintain distinct connectivity throughout their lifetime.

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Hippocampal hub neurons maintain distinct connectivity throughout their lifetime.

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