Saccadic omnipause and burst neurons in monkey and human are ensheathed by perineuronal nets but differ in their expression of calcium‐binding proteins

Abstract

The extracellular matrix of the brain contains large aggregates of chondroitin sulfate proteoglycans (CSPG), which form lattice-like cell coatings around distinct neuron populations and are termed perineuronal nets. The function of perineuronal nets is not fully understood, but they are often found around neurons containing the calcium-binding protein parvalbumin, suggesting a function in primarily highly active neurons. In the present paper the distribution of perineuronal nets was studied in two functional cell groups of the primate oculomotor system with well-known firing properties: 1) the saccadic omnipause neurons in the nucleus raphe interpositus (RIP) exhibit a high tonic firing rate, which is only interrupted during saccades; they are inhibitory and use glycine as a transmitter; and 2) premotor burst neurons for vertical saccades in the rostral interstitial nucleus of the medial longitudinal fascicle (RiMLF) fire with high-frequency bursts during saccades; they are excitatory and use glutamate and/or aspartate as a transmitter. In the macaque monkey, both cell populations were identified by their parvalbumin immunoreactivity and were studied for the presence of perineuronal nets using CSPG antibodies or lectin binding with Wisteria floribunda agglutinin. In addition, the expression of another calcium-binding protein, calretinin, was studied in both cell groups. Double- and triple-immunofluorescence methods revealed that both omnipause and burst neurons are selectively ensheathed with strongly labeled perineuronal nets. Calretinin was coexpressed in at least 70% of the saccadic burst neurons, but not in the omnipause neurons. Parallel staining of human tissue revealed strongly labeled perineuronal nets around the saccadic omnipause and burst neurons, in corresponding brainstem regions, which specifically highlighted these neurons within the poorly structured reticular formation. These findings support the hypothesis that perineuronal nets may provide a specialized microenvironment for highly active neurons to maintain their fast-spiking activity and are not related to the transmitter or the postsynaptic action of the ensheathed neurons.

Perioculomotor cell groups in monkey and man defined by their histochemical and functional properties: Reappraisal of the Edinger‐Westphal nucleus

“…The simultaneous absence of both markers supports a current hypothesis proposing that perineuronal net labeling is preferentially associated with markers for highly active neurons (Brü ckner et al, 1993) such as parvalbumin (Hä rtig et al, 1994;Morris and Henderson, 2000), the expression of the voltage-dependent potassium channel subunit Kv3.1b , or cytochrome oxidase (Blü mcke and Celio, 1992). These relationships have also been shown for cell groups of the saccadic system (Horn et al, 2003), whereas slow-firing aminergic neurons in the substantia nigra, raphe nuclei, and locus coeruleus lack perineuronal nets (Hobohm et al, 1998). This also fits with the pIII U population, in that in vitro recording experiments within the UCN-positive cell group in rat indicated slow firing rates of the neurons (Laursen and Rekling, 2006).…”

Purkinje cell axon collaterals terminate on Cat-301+ neurons in Macaca monkey cerebellum

“…The functional consequences of 'locking' PC synapses to a neuron at an early postnatal age would be reflected in the neuron's post-synaptic contacts. Elsewhere in the brain, neurons with PNNs have been shown to contribute to the demarcation of specific cortical maps Bruckner et al, 1999;Adams et al, 2001;Horn et al, 2003). For example, in human primary and secondary visual cortex Cat-301 labeling correlates with the organization of ocular dominance columns and the magnocellular pathway .…”

“…PNNs are expressed after birth during critical periods of development for neuronal wiring (Kalb and Hockfield, 1990a,b; Pizzorusso et al, 2002;Yin et al, 2006). Probable functions include neuro-protection, organization of cortical compartments, stabilization of synaptic contacts and inhibition of axonal sprouting (Bruckner et al, 1993; Matthew et al, 2002;Carulli et al, 2006;Margolis and Margolis, 1997; Pizzorusso et al, 2002;Horn et al, 2003;Rhodes and Fawcett, 2004;;Yin et al, 2006). Conversely, the break down of PNNs has been shown in studies throughout the brain to be a necessary step to promote central and peripheral nervous system repair (Berardi Corresponding author: F.R.…”

Subpopulations of neurons expressing parvalbumin in the human amygdala

“…The possibility that at least some of the -/PNN/-neurons in the amygdala may be glutamatergic projection neurons is supported by descriptions of PNN-positive, glutamate-IR pyramidal neurons in the rodent cortex (Wegner et al, 2003). In either case, the strong association between PNNs and "highly active" neurons (Horn et al, 2003) suggests that -/ PNN/-neurons might represent a distinct neuronal subpopulation characterized by a high firing rate. …”