Altered Excitability and Glutamatergic Synaptic Transmission in the Medium Spiny Neurons of the Nucleus Accumbens in Mice Deficient in the Heparan Sulfate Endosulfatase <i>Sulf1</i>

Sulf1 is an extracellular sulfatase that regulates cell signaling by removing 6-<i>O</i>-sulfates from heparan sulfate. Although the roles of <i>Sulf1</i> in neural development have been studied extensively, its functions in the adult brain remain largely unknown. Here, we report the effects of <i>Sulf1</i> disruption on the neuronal properties of the medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell, one of the regions highly expressing <i>Sulf1</i> We separately labeled MSNs expressing dopamine D1 receptors (D1-MSNs) or D2 receptors (D2-MSNs) by injecting adult male <i>Drd1-Cre</i> and <i>Drd2-Cre</i> mice with a Cre-dependent AAV vector expressing a red fluorescent protein, mCherry, and examined their electrophysiological properties by means of whole-cell patch-clamp recording. In the D2-MSNs, <i>Sulf1</i> disruption led to drastic changes in neural firing responses to depolarizing current injections: in the <i>Sulf1</i> knock-out mice, the rheobase was smaller than in the wild-type mice, but the number of action potentials elicited by depolarization did not increase at larger current injections. In the D1-MSNs, <i>Sulf1</i> disruption resulted in more depolarized resting membrane potentials and increase in the AMPA/NMDA ratio. These results suggest that <i>Sulf1</i> is essential for regulation of neuronal excitability and glutamatergic transmission of NAc MSNs in adult mice and implicate the potential roles of <i>Sulf1</i> in NAc circuit activity, reward-aversion behaviors, and psychiatric disorders such as schizophrenia and drug addiction.