Distinct Lineage-Dependent Structural and Functional Organization of the Hippocampus

Abstract

SUMMARY The hippocampus, as part of the cerebral cortex, is essential for memory formation and spatial navigation. Although it has been extensively studied, especially as a model system for neurophysiology, the cellular processes involved in constructing and organizing the hippocampus remain largely unclear. Here, we show that clonally related excitatory neurons in the developing hippocampus are progressively organized into discrete horizontal, but not vertical, clusters in the stratum pyramidale, as revealed by both cell type-specific retroviral labeling and mosaic analysis with double markers (MADM). Moreover, distinct from those in the neocortex, sister excitatory neurons in Cornu Ammonis 1 region of the hippocampus rarely develop electrical or chemical synapses with each other. Instead, they preferentially receive common synaptic input from nearby fast-spiking (FS), but not non-FS, interneurons and exhibit synchronous synaptic activity. These results suggest that shared inhibitory input may specify horizontally clustered sister excitatory neurons as functional units in the hippocampus.

Construction of functional neuronal circuitry in the olfactory bulb

“…It has been reported that the birthdate of mitral cells is a determinant of neuronal circuitry: early-born and late-born mitral cells tend to locate in the dorsal and ventral OB, respectively, and late-born neurons tend to project their axons to olfactory tubercle [36]. It will also be interesting to test whether cell lineage specify some aspects of wiring specificity of mitral cells, as has been reported in the cerebral cortex [37][38][39] (but see also [40]). Alternatively, mitral/tufted cells may be naïve without inputs and their wiring specificity may be established based on OSN inputs after stochastically choosing one target glomerulus.…”

Place cells in the hippocampus: Eleven maps for eleven rooms

“…Developmental studies indicate that, through direct or indirect connections, hippocampal cells form synapses preferentially with cells from the same clone (15,16). Clustering of connectivity might point to an architecture of discrete subpopulations that have different functional properties.…”

“…Recent observations suggest, however, that hippocampal network activity is to some extent preconfigured. The hippocampus contains cell populations with distinct developmental histories that interconnect selectively within as well as between hippocampal subfields (15,16). Such clusters of interconnected neurons may limit the number and variability of place-cell ensembles that can be formed when animals encounter new environments.…”

CA1 pyramidal cell diversity enabling parallel information processing in the hippocampus

“…In addition, neocortical migrating neurons typically proceed using a single radial fiber as scaffold, whereas migrating future hippocampal pyramidal neurons use multiple radial glial fibers and migrate considerably more slowly 137 . Furthermore, clonally related CA1 neurons are distributed in a more horizontal manner, not in a well-defined vertical column as in the case of neocortical PCs 109 . The obscuring of the basic inside-out pattern may be related to the ongoing horizontal expansion of the relatively thin hippocampal plate during development, which may make it difficult for clonally related cells to be strictly vertically aligned 137 .…”

“…Are they formed during development or are they principally shaped by activity-dependent plasticity mechanisms? A role for developmental processes has been recently demonstrated in the formation of preferentially interconnected fast-spiking basket cells and the CA1PC subgroups 109 , where clonally related sister CA1PC pairs do not preferentially form synapses with each other but fast-spiking cells provide common GABAergic synaptic inputs selectively to sister CA1PCs. Such preferential innervation of clonally related CA1PCs could underlie the observed synchronous activity in sister cells and indicate that the foundations of the biased excitatory–inhibitory local network motifs are at least partly established during development.…”