Early-life adversity selectively interrupts the dendritic differentiation of dorsolateral striatal neurons in male mice

Abstract

The effects of early-life adversity (ELA) on dendritic differentiation of striatal neurons were investigated in the dorsal striatum including the dorsomedial striatum and dorsolateral striatum (DMS and DLS, respectively). An animal model of ELA was created by changing the growth environment of newborn mouse pups by giving limited bedding and nesting materials from postnatal day 2 to day 9 (P2-P9). One week after the stress paradigm (P16), the dendritic branches and spines of striatal spiny neurons as well as the synapses represented by postsynaptic density protein-95 (PSD-95) in DMS and DLS were stereologically analyzed. Adverse experience in early life selectively affected the spiny neurons in DLS, leading to abundant proximal dendritic branches and an increased number of filopodia-like protrusions, but a reduced number of dendritic spines. The selective effects of stress on neurons in DLS were further identified by reduced expression of PSD-95, including a reduced optical density of PSD-95 immunoreactivity and fewer individual PSD-95 immunoreactive synapses in this region. Notably, stress in early life affected either D1 or D2 dopamine receptor-expressing DLS neurons. These findings suggest that adverse early-life experience delayed the maturation of dendritic spines on neurons in the dorsolateral striatum. Altered dendritic differentiation provoked by stress in early life may contribute critically to the formation of proper neuronal circuits in the dorsal striatum and, therefore, affect striatum-dependent habitual behavior and emotional function later in life.

Keywords: D1; D2 dopamine receptors; Dendritic spine; Dorsal striatum; Early-life stress; Mouse; Synapse.