Abstract
N-methyl-D-aspartate receptors (NMDARs) are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play an important role in the adult structural plasticity of excitatory neurons, but their impact on the remodeling of interneurons is unknown. Among hippocampal interneurons, somatostatin-expressing cells located in the stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change density in response to different stimuli. In order to understand the role of NMDARs on the structural plasticity of these interneurons, we have injected acutely MK-801, an NMDAR antagonist, to adult mice which constitutively express enhanced green fluorescent protein (EGFP) in these cells. We have behaviorally tested the animals, confirming effects of the drug on locomotion and anxiety-related behaviors. NMDARs were expressed in the somata and dendritic spines of somatostatin-expressing interneurons. Twenty-four hours after the injection, the density of spines did not vary, but we found a significant increase in the density of their en passant boutons (EPB). We have also used entorhino-hippocampal organotypic cultures to study these interneurons in real-time. There was a rapid decrease in the apparition rate of spines after MK-801 administration, which persisted for 24 h and returned to basal levels afterwards. A similar reversible decrease was detected in spine density. Our results show that both spines and axons of interneurons can undergo remodeling and highlight NMDARs as regulators of this plasticity. These results are specially relevant given the importance of all these players on hippocampal physiology and the etiopathology of certain psychiatric disorders.
Highlights
The study of changes in the morphology of neurons is important for understanding neural activity
In order to analyze the functionality of enhanced green fluorescent protein (EGFP) + en passant boutons (EPB), we studied the presence of gephyrin-expressing puncta (GEPH) in juxtaposition with these presynaptic structures
The N-methyl-D-aspartate receptors (NMDARs) are among the most studied receptors in the nervous system, because of their involvement in LTP and several developmental processes (Butler et al, 1998; McKinney et al, 1999b; Nacher and McEwen, 2006; Kehoe et al, 2014). These receptors play an important role in the activity-dependent regulation of the morphology of the dendritic spines of excitatory neurons (Nikonenko et al, 2002; Ultanir et al, 2007)
Summary
The study of changes in the morphology of neurons is important for understanding neural activity. Dendritic spines are membranous protrusions, which can establish excitatory or inhibitory synapses through different neurotransmitter receptors. They were thought to be a distinctive feature of principal neurons, different studies have shown that some interneuronal subpopulations display these postsynaptic specializations (Freund and Buzsáki, 1996). Boutons are axonal thickenings, which contain and release the synaptic vesicles Because of their roles as postsynaptic and presynaptic elements, spines and boutons have been found to be proper markers for neuronal input and output; increases in spine and axonal bouton density have been correlated to increases in neuronal activity (Engert and Bonhoeffer, 1999; Becker et al, 2008)
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