Elsevier

Experimental Neurology

Volume 275, Part 2, January 2016, Pages 245-252
Experimental Neurology

Neonatal sensory nerve injury-induced synaptic plasticity in the trigeminal principal sensory nucleus

https://doi.org/10.1016/j.expneurol.2015.04.022Get rights and content

Highlights

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    Neonatal sensory nerve damage alters sensory maps in the CNS and results in substantial synaptic reorganization.

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    In rats and mice, neonatal infraorbital nerve lesions lead to conversion of functional synapses to silent synapses.

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    Sensory nerve damage causes convergence of multipletrigeminal afferents on single neurons in the trigeminal brainstem.

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    Injury-induced synaptic plasticity does not follow the timing ofthe critical period for structural plasticity.

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    Effects of neonatal sensory nerve transection and crushare quite different in the CNS.

Abstract

Sensory deprivation studies in neonatal mammals, such as monocular eye closure, whisker trimming, and chemical blockade of the olfactory epithelium have revealed the importance of sensory inputs in brain wiring during distinct critical periods. But very few studies have paid attention to the effects of neonatal peripheral sensory nerve damage on synaptic wiring of the central nervous system (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory afferents in that they are more prone to crush or severance because of their locations in the body. Unlike the visual and auditory afferents, these nerves show regenerative capabilities after damage. Uniquely, damage to a somatosensory peripheral nerve does not only block activity incoming from the sensory receptors but also mediates injury-induced neuro- and glial chemical signals to the brain through the uninjured central axons of the primary sensory neurons. These chemical signals can have both far more and longer lasting effects than sensory blockade alone. Here we review studies which focus on the consequences of neonatal peripheral sensory nerve damage in the principal sensory nucleus of the brainstem trigeminal complex.

Section snippets

Neonatal sensory nerve damage

Obstetric injuries to the brachial plexus during birth and orofacial injuries and fractures in young children are common occurrences which can lead to permanent brachial plexus palsy or trigeminal nerve pathologies (see reviews by Alcalá-Galiano et al., 2008, Eggensperger Wymann et al., 2008, Sandmire et al., 2008). While these neurological cases are extensively studied at the peripheral nerve level, their CNS consequences remain largely unknown. In pain research, drastic changes in the

Development and organization of the rodent trigeminal system and the PrV

The infraorbital (IO) branch of the maxillary division of the trigeminal nerve is an exclusively sensory nerve. The IO innervates all of the whiskers on the snout. Central axons of the ION convey whisker-specific information to the trigeminal brainstem. Through interaction of target-derived molecular cues and receptors, the trigeminal ganglion (TG) neurons that contribute to the ION establish a topographic and patterned map of the whisker follicles in the trigeminal brainstem (reviewed in

Physiological properties of the PrV neurons

The ventral PrV contains three classes of neurons: (1) Barrelette cells, (2) Interbarrelette cells, and (3) inhibitory interneurons. Polarized, asymmetrical dendritic orientation and whisker-specific patterning are morphological characteristics of barrelette neurons. These cells can be distinguished further by their electrophysiological properties (Fig. 2). They display a transient K+ (IA) current and receive monosynaptic excitatory and disynaptic inhibitory inputs when the trigeminal tract is

Effects of neonatal ION transection on physiological properties of the PrV

The unique whisker-specific neural patterning, which starts in the PrV and ends in the SI cortex, takes place during a short period in the late embryonic and the early postnatal periods. Damage to the ION or whisker follicle cautery during postnatal (P) life up to day 3 irreversibly alters the patterning of the system (reviewed in Erzurumlu and Gaspar, 2012, Erzurumlu and Kind, 2001) (Fig. 3). Since the pioneering study by Van der Loos and Woolsey (1973), several groups have repeatedly

Peripheral nerve injury-induced reactive synaptogenesis in the CNS

In the mature CNS, denervation results in rapid synaptic loss followed by a prolonged period of new synapse formation. This form of neural plasticity has been referred to as “reactive synaptogenesis,” implying that it is a reaction to denervation (Collazos-Castro and Nieto-Sampedro, 2001, Cotman et al., 1981, Hamori, 1990, Matthews et al., 1976). In the mature state, the time course of reactive synaptogenesis varies among different central pathways. For example, in the entorhinal cortex–dentate

“Silent” synapses in the deafferented PrV

Failure to form or dissolution of whisker-specific barrelette patterns in the denervated PrV is accompanied by an increase in afferent convergence upon individual barrelettes cells. Paradoxically, this TG input convergence does not entail functional synapses. In fact, most functional synapses convert to silent synapses (Lo and Erzurumlu, 2007). Silent synapses have been identified as synapses, which show NMDA, but an absence of AMPA receptor response in hippocampal and cortical slices (Isaac et

Aftermath of crush injuries and nerve regeneration

A question of clinical significance begs whether or not these structural and functional changes are reversible after regeneration of ION fibers. Unfortunately, the regeneration of sectioned ION is a slow process and never complete (Jeno and László, 2002, Kis et al., 1999, Renehan and Munger, 1986, Waite, 1984, Waite and Cragg, 1982) Nevertheless, crush injury leads to a partial blockade of nerve function and rapid functional recovery by detecting postsynaptic responses induced by peripheral

Mechanisms of peripheral nerve injury-induced synaptic plasticity in the CNS

What are the mechanisms underlying synaptic plasticity in the CNS following peripheral nerve injury? A fortuitous observation in the Prv following neonatal ION injury is a dramatic increase in astrocytosis, evidenced by glial fibrillary acidic protein (GFAP) immunostaining (Lo et al., 2011, Lo et al., 2014) (Fig. 4). Astrocytes play an active role in the development and maintenance of synapses and in reactive synaptogenesis following brain injury (Ullian et al., 2004). In vitro studies show

Transsynaptic responses to neonatal sensory nerve damage

When sensory nerve damage alters synaptic circuitry at the first relay station in the CNS it is not difficult to envisage that other downstream target regions might also be affected. Surprisingly, very little is known about transregional effects of neonatal ION lesions, other than transsynaptic cell death and loss of whisker-specific neuronal patterns. Ongoing studies in our laboratory show that neonatal ION damage leads to silent synapses in the VPM and convergence of multiple PrV afferent

Conclusions

The neonatal brain is highly malleable and responds to peripheral sensory nerve injury by altered connectivity and synaptic arrangements. Some of these altered circuitry functions can be reversed while others are changed irreversibly. The laboratory rodent whisker–barrel system is an excellent model to investigate peripheral nerve injury-induced synaptic plasticity in the neonatal brain.

Both transection and crush injuries of the infraorbital nerve, a purely sensory nerve, lead to dissolution of

Conflict of interest

The authors declare no conflict of interest.

Acknowledgments

We thank Ms. S. Zhao for excellent technical assistance with histological materials and photomicroscopy. Research in our laboratory is supported by NIH NS039050.

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