Potential Synaptic Connectivity of Different Neurons onto Pyramidal Cells in a 3D Reconstruction of the Rat Hippocampus

Deepak Ropireddy,Giorgio A Ascoli

doi:10.3389/fninf.2011.00005

Abstract

Most existing connectomic data and ongoing efforts focus either on individual synapses (e.g., with electron microscopy) or on regional connectivity (tract tracing). An individual pyramidal cell (PC) extends thousands of synapses over macroscopic distances (∼cm). The contrasting requirements of high-resolution and large field of view make it too challenging to acquire the entire synaptic connectivity for even a single typical cortical neuron. Light microscopy can image whole neuronal arbors and resolve dendritic branches. Analyzing connectivity in terms of close spatial appositions between axons and dendrites could thus bridge the opposite scales, from synaptic level to whole systems. In the mammalian cortex, structural plasticity of spines and boutons makes these “potential synapses” functionally relevant to learning capability and memory capacity. To date, however, potential synapses have only been mapped in the surrounding of a neuron and relative to its local orientation rather than in a system-level anatomical reference. Here we overcome this limitation by estimating the potential connectivity of different neurons embedded into a detailed 3D reconstruction of the rat hippocampus. Axonal and dendritic trees were oriented with respect to hippocampal cytoarchitecture according to longitudinal and transversal curvatures. We report the potential connectivity onto PC dendrites from the axons of a dentate granule cell, three CA3 PCs, one CA2 PC, and 13 CA3b interneurons. The numbers, densities, and distributions of potential synapses were analyzed in each sub-region (e.g., CA3 vs. CA1), layer (e.g., oriens vs. radiatum), and septo-temporal location (e.g., dorsal vs. ventral). The overall ratio between the numbers of actual and potential synapses was ∼0.20 for the granule and CA3 PCs. All potential connectivity patterns are strikingly dependent on the anatomical location of both pre-synaptic and post-synaptic neurons.

Highlights

Mammalian brains have complex network architectures (Sporns, 2010), with each neuron connecting to thousands of others
The results presented here are intended as a proof-of-concept of the 3D framework in computing the full potential connectivity of single neurons throughout system-level regional maps
The approach introduced here enables the analysis of potential connectivity patterns from individual axo-dendritic overlaps across the entire hippocampus

Summary

Introduction

Mammalian brains have complex network architectures (Sporns, 2010), with each neuron connecting to thousands of others. Connectivity must be characterized at both synaptic and regional levels to advance our knowledge of cognitive and computational functions of nervous systems (Sporns et al, 2005; Buzsaki, 2007). Numerous studies recently explored structural and functional connectivity with different experimental modalities, including non-invasive imaging (Bullmore and Sporns, 2009; Honey et al, 2009; Bressler and Menon, 2010), electrophysiology (Kalisman et al, 2005), light microscopy (Ishizuka et al, 1990; Sik et al, 1993; Li et al, 1994; Wittner et al, 2007), and electron microscopy (Mishchenko et al, 2010). Non-invasive imaging such as DTI allows investigation of the whole human brain, but is only amenable to analyzing regional connectivity. Light microscopy provides an optimal balance of resolution and field of view for this neuronal connectomic level bridging the micro- and macro-scale

Methods

Results

Conclusion