ReviewDoes the brain connect before the periphery can direct?: A comparison of three sensory systems in mice
Introduction
Neural circuits begin to form during early brain development at embryonic ages. Whether each synaptic relay of the circuit forms autonomously or is directed in some fashion by a previous relay is a key issue and is typically addressed by investigating whether neural activity plays a role in neural development. Here we evaluate the more general question of whether neural signaling, including both electrical and synaptic activity but also non-synaptic biochemical interactions between neurons and along neural pathways, drives circuit formation. This issue is more easily approached in sensory systems because the primary direction of information transfer is specified, in that neural activity originates in the peripheral sensory organ and propagates along neural circuits in the CNS. One means to answer the question of whether sensory systems connect from periphery to cortex, or specifically, does one synaptic relay drive patterning and neural connectivity at subsequent relays, is to examine whether central contacts between neurons form and are functional prior to ability of the sensory periphery to transmit information to more central structures. In this context we evaluate when cellular processes first reach the vicinity of cells with which they will later form classical synaptic contacts. We explored this issue by comparing three relay stations of the ascending neural circuit in sensory systems: (1) receptor cells and associated neurons including ganglion cells, (2) first order CNS target neurons of the sensory ganglion neurons, and (3) second order CNS target neurons of the first order CNS neurons. We present and consider the state of knowledge for three well-studied sensory systems, the auditory, visual and olfactory systems. Given an increasing emphasis on the mouse model for studies of nervous system development, we focus our presentation on data from that species. For each sensory system, we present the birthdates of the circuit-forming cells and information about the structural and functional development of these selected neural connections. We evaluate when the anatomical substrate for each functional connection is established by reporting the earliest evidence from light and/or electron microscopy (EM) studies. We then present the earliest evidence for functional synaptic connections based on electrophysiological recordings, induced expression of immediate early genes, or behavioral readouts of appropriate sensory stimulation.
Although the auditory, visual and olfactory systems are similar in basic organization, they differ in detail. The olfactory system is simplest in peripheral organization, in that the olfactory sensory neuron (OSN) forms the olfactory nerve (without an intervening synapse) and so projects directly into the CNS. The auditory system incorporates a synaptic connection between the receptor cell, or hair cell, and peripheral ganglion cell whose axons form the auditory nerve projection into the CNS. The visual system is most complex in its peripheral organization, whereby the retina is a multi-layered neural network that is part of the CNS, with multiple synaptic connections preceding input to ganglion cells whose axons form the optic nerve projection to the thalamus and other central targets. For the visual and olfactory pathways presented here, the first order target neurons of their respective ganglion neurons project directly to sensory cortex. In contrast, the auditory system has at least four processing stations interposed between the first order CNS target of the auditory nerve and auditory cortex. The systems differ also in the onset of sensitivity to external environmental stimuli. The olfactory system is exposed to airborne odorants at birth, but the auditory and visual systems are not engaged fully until airborne sound is capable of eliciting action potentials in the auditory nerve at postnatal day (P)9 (Mikaelian and Ruben, 1965) and the eyes open at P13–14 (Poole, 1987).
The purpose of this article is to describe and compare the initial formation of synaptic contacts among these three sensory systems. Refinement of central connections that is dependent on neural activity is beyond the scope of this presentation, and we refer the reader to the following references that describe refinement in the auditory (Huang et al., 2007, Kandler, 2004, Rubel et al., 1998), visual (Hooks and Chen, 2007, Huberman et al., 2008, Torborg and Feller, 2005), and olfactory systems (Schwob et al., 1984, Schwob and Price, 1984, Zou et al., 2004). Although this review is focused upon comparisons among sensory systems in the mouse, references to other rodent species are made where data from mouse are incomplete. We found that many questions regarding the timing and nature of neural circuit formation in these systems remain open, so a key purpose of this presentation is to highlight topics that merit further study.
Section snippets
Auditory system
The three circuit connections that we consider for the auditory system are: (1) the connection between the inner hair cell and primary afferent spiral ganglion neuron, (2) the connection between the spiral ganglion neuron and a subdivision of its target cell group in the CNS, the ventral subdivision of the cochlear nucleus (VCN), and (3) the connection between the VCN and the next processing station in the auditory pathway, the superior olivary complex (SOC) located in the core of the brainstem
Visual system
Of the three sensory organs discussed here, the neuronal architecture within the eye is the most complex in terms of cell types, circuitry and processing. Therefore, for the purpose of this review, we focus on the following retinal circuits that together comprise the initial connections in the visual system: (1a) photoreceptor connections onto bipolar cells, (1b) bipolar cell connections onto retinal ganglion cells (RGCs), and (1c) amacrine cell synapses onto RGCs. For the sake of simplicity,
Olfactory system
Olfaction initiates in the nasal epithelium where combinations of olfactory sensory neurons (OSNs) reside, each encoding a single receptor subtype that selectively binds to a particular odorant molecule (Bozza et al., 2002, Buck and Axel, 1991, Chess et al., 1994). The mouse genome encodes approximately 1200 different OSN receptor types for OSNs. Although OSN cell types are relatively scattered across 4 epithelial zones, OSN axons are targeted by individual receptor type to particular mitral
Unresolved issues in sensory system development
The title of this article posed the question: does the brain connect before the periphery can direct?
Multiple observations might suggest it does. Soon after final mitosis, many neurons extend an axon toward their target even as their cell body migrates toward its final position in the brain (Yee et al., 1999). Axon guidance cues then position the axon growth cone into an approximate location to innervate its target (Tessier-Lavigne and Goodman, 1996). The role of neurotransmitter release in
Acknowledgments
Portions of this work were supported by National Institutes of Health (NIH) grants F32 DC008730 to BH, RO1 DC007695 to GS, RO1 EY012152 to PM and a NIH/NCRR COBRE grant P20 RR15574 to the Sensory Neuroscience Research Center.
References (133)
- et al.
Mice deficient in G(olf) are anosmic
Neuron
(1998) - et al.
Calcium dependence of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse
Neuron
(2001) - et al.
A novel multigene family may encode odorant receptors: a molecular basis for odor recognition
Cell
(1991) - et al.
Development of precise maps in visual cortex requires patterned spontaneous activity in the retina
Neuron
(2005) - et al.
Allelic inactivation regulates olfactory receptor gene expression
Cell
(1994) - et al.
Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map
Cell
(2003) - et al.
Early cortical histogenesis in the primary olfactory cortex of the mouse
Brain Res.
(1977) - et al.
Dynamic processes shape spatiotemporal properties of retinal waves
Neuron
(1997) - et al.
Development of olfactory receptor neuron selectivity in the rat fetus
Neuroscience
(1982) - et al.
Role of class D L-type Ca2+ channels for cochlear morphology
Hear. Res.
(2003)