The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held.

KEY POINTS: The proteoglycan brevican is a major component of the extracellular matrix of perineuronal nets and is highly enriched in the perisynaptic space suggesting a role for synaptic transmission. We have introduced the calyx of Held in the auditory brainstem as a model system to study the impact of brevican on dynamics and reliability of synaptic transmission. In vivo extracellular single-unit recordings at the calyx of Held in brevican-deficient mice yielded a significant increase in the action potential (AP) transmission delay and a prolongation of pre- and postsynaptic APs. The changes in dynamics of signal transmission were accompanied by the reduction of presynaptic vGlut1 and ultrastructural changes in the perisynaptic space. These data show that brevican is an important mediator of fast synaptic transmission at the calyx of Held. ABSTRACT: The extracellular matrix is an integral part of the neural tissue. Its most conspicuous manifestation in the brain are the perineuronal nets (PNs) which surround somata and proximal dendrites of distinct neuron types. The chondroitin sulfate proteoglycan brevican is a major component of PNs. In contrast to other PN-comprising proteoglycans (e.g. aggrecan and neurocan), brevican is mainly expressed in the perisynaptic space closely associated with both the pre- and postsynaptic membrane. This specific localization prompted the hypothesis that brevican might play a role in synaptic transmission. In the present study we specifically investigated the role of brevican in synaptic transmission at a central synapse, the calyx of Held in the medial nucleus of the trapezoid body, by the use of in vivo electrophysiology, immunohistochemistry, biochemistry and electron microscopy. In vivo extracellular single-unit recordings were acquired in brevican-deficient mice and the dynamics and reliability of synaptic transmission were compared to wild-type littermates. In knockout mice, the speed of pre-to-postsynaptic action potential (AP) transmission was reduced and the duration of the respective pre- and postsynaptic APs increased. The reliability of signal transmission, however, was not affected by the lack of brevican. The changes in dynamics of signal transmission were accompanied by the reduction of (i) presynaptic vGlut1 and (ii) the size of subsynaptic cavities. The present results suggest an essential role of brevican for the functionality of high-speed synaptic transmission at the calyx of Held.

Paternal deprivation alters region- and age-specific interneuron expression patterns in the biparental rodent, Octodon degus.

The impact of paternal care on the postnatal development of inhibitory neuronal subpopulations in prefrontal and limbic brain regions was studied in the rodent Octodon degus. Comparing offspring from biparental families with animals raised by a single mother revealed region-specific deprivation-induced changes in the density of PARV- and CaBP-D28k expressing cells. Some deprivation-induced changes were only seen at P21: elevated CaBP-D28k-positive neurons in the orbitofrontal cortex, CA1, CA3, and dentate gyrus (DG) and elevated PARV-positive neurons in the lateral orbitofrontal, prelimbic/infralimbic (PL/IL), DG and CA1, nucleus accumbens, and amygdala. Some deprivation-induced changes were obvious in both age groups: increased CaBP-D28k-positive neurons in the nucleus accumbens shell and increased PARV-positive neurons in the ventral orbitofrontal. Some deprivation-induced changes were only seen in adulthood: increased CaBP-D28k-positive neurons in the amygdala and decreased PARV-positive neurons in the PL/IL and in CA3. In CA1, PARV-positive neurons were increased at P21 and decreased in adulthood. The functional significance of the deprivation-induced changes in PARV-positive neurons, which are involved in gamma oscillations and thereby affect information processing and which appear to be key players for critical period plasticity in sensory cortex development, as well as the behavioral implications remain to be further elucidated.