Perineuronal nets labeled by monoclonal antibody VC1.1 ensheath interneurons expressing parvalbumin and calbindin in the rat amygdala

Abstract

Perineuronal nets (PNNs) are specialized condensations of extracellular matrix that ensheath particular neuronal subpopulations in the brain and spinal cord. PNNs regulate synaptic plasticity, including the encoding of fear memories by the amygdala. The present immunohistochemical investigation studied PNN structure and distribution, as well as the neurochemistry of their ensheathed neurons, in the rat amygdala using monoclonal antibody VC1.1, which recognizes a glucuronic acid 3-sulfate glycan associated with PNNs in the cerebral cortex. VC1.1+ PNNs surrounded the cell bodies and dendrites of a subset of nonpyramidal neurons in cortex-like portions of the amygdala (basolateral amygdalar complex, cortical nuclei, nucleus of the lateral olfactory tract, and amygdalohippocampal region). There was also significant neuropilar VC1.1 immunoreactivity whose density varied in different amygdalar nuclei. Cell counts in the basolateral nucleus revealed that virtually all neurons ensheathed by VC1.1+ PNNs were parvalbumin-positive (PV+) interneurons, and these VC1.1+/PV+ cells constituted 60% of all PV+ interneurons, including all of the larger PV+ neurons. Approximately 70% of VC1.1+ neurons were calbindin-positive (CB+), and these VC1.1+/CB+ cells constituted about 40% of all CB+ neurons. Colocalization of VC1.1 with Vicia villosa agglutinin (VVA) binding, which stains terminal N-acetylgalactosamines, revealed that VC1.1+ PNNs were largely a subset of VVA+ PNNs. This investigation provides baseline data regarding PNNs in the rat which should be useful for future studies of their function in this species.

WFA-labeled perineuronal nets in the macaque claustrum

“…In the rat basolateral nucleus of the amygdala, all PNN ensheathed neurons were PV+; but that population, of PNN+PV+ neurons, comprised only 60% of all PV+ interneurons. Similar results were obtained for calbindin+ neurons in the amygdala [16]. In the mouse hippocampus, PNNs surround 90% of PV+ basket cells, 25–50% of PV+ bistratified cells, but only minor proportions of other PV+ cell types [6, 29].…”

“…Although some excitatory neurons are enwrapped by PNNs, these more commonly are associated with parvalbumin-positive (PV+) and other inhibitory neurons [13–16]. A large proportion of the neurons in the reticular nucleus (RT) of the thalamus, for example, are associated with PNNs, so that this structure is one of the most darkly stained regions.…”

The extracellular matrix and perineuronal nets in memory

“…CA2 also participates in social novelty discrimination [ 128 ] and modulates social aggression [ 129 ]. All the social memory associated regions are highly populated with PNN-surrounded PV neurons [ 46 , 66 , 130 , 131 ]. Unusually in CA2 and the basolateral amygdala, PNNs are found around many excitatory pyramidal cells [ 47 , 66 ], and calbindin-positive inhibitory interneurons [ 130 ].…”

“…All the social memory associated regions are highly populated with PNN-surrounded PV neurons [ 46 , 66 , 130 , 131 ]. Unusually in CA2 and the basolateral amygdala, PNNs are found around many excitatory pyramidal cells [ 47 , 66 ], and calbindin-positive inhibitory interneurons [ 130 ]. PNNs play a distinct role in social memory, since mice with deficient social memory (BTBR mice) have atypical PNNs, and their degradation can partially restore social memory [ 132 ].…”

Chronic fluoxetine treatment impairs motivation and reward learning by affecting neuronal plasticity in the central amygdala

“…Notably, involvement of MMP‐9 in degradation of perineuronal nets has been well documented in both animal models and human patients (Alaiyed, Bozzelli, Caccavano, Wu, & Conant, 2019; Alaiyed & Conant, 2019; Brunswick et al, 2002; Gray, Thomas, Betmouni, Scolding, & Love, 2008; Lorenzo Bozzelli, Alaiyed, Kim, Villapol, & Conant, 2018; Murase, Lantz, & Quinlan, 2017; Pollock, Everest, Brown, & Poulter, 2014; Wen, Binder, Ethell, & Razak, 2018). The perineuronal nets preferentially surround inhibitory neurons (Härtig, Brückner, Brauer, Schmidt, & Bigl, 1995; Morris & Henderson, 2000; Naegele, Arimatsu, Schwartz, & Barnstable, 1988; Naegele & Katz, 1990; Seeger, Brauer, Härtig, & Brückner, 1994), such as those expressing PV and calbindin (CALB) (Lensjø, Christensen, Tennøe, Fyhn, & Hafting, 2017; McDonald, Hamilton, & Barnstable, 2018; Ohira, Takeuchi, Iwanaga, & Miyakawa, 2013; Vidal et al, 2006). The disruption of the interplay between the perineuronal nets surrounding these cells and MMP‐9 is thought to contribute to numerous neuropsychiatric and neurodegenerative disorders, including schizophrenia, Alzheimer's disease and epilepsy (Wen, Binder, Ethell, & Razak, 2018).…”