Differential electrophysiological properties of D1 and D2 spiny projection neurons in the mouse nucleus accumbens core

Abstract

The striatum consists of the dorsal (caudate/putamen) and the ventral (nucleus accumbens) regions. The nucleus accumbens is further divided into a core and shell. Both the dorsal and ventral striatum contain populations of spiny projection neurons, which make up 95% of the neurons within the striatum. SPNs are canonically categorized into those that express the D1‐type dopamine receptor (D1 SPNs) and those that express the D2‐type dopamine receptor (D2 SPNs). D1 and D2 SPNs differ with respect to both synaptic inputs and projection targets. In the dorsal striatum, it is well established that these populations of SPNs differ in terms of their electrophysiological and morphological properties. However, there remains a gap in our knowledge of the electrophysiological properties of SPNs in the nucleus accumbens core. To evaluate the differential properties of these SPNs, we performed whole‐cell recordings from D1 and D2 SPNs in BAC transgenic mice in which D1 SPNs fluoresce red and D2 SPNs fluoresce green. The two SPN subtypes did not differ in terms of their time constant, capacitance, resting membrane potential, or tonic current. However, D2 SPNs displayed heightened inhibitory postsynaptic current (IPSC) and miniature excitatory PSC frequency as compared with D1 SPNs. Furthermore, D2 SPNs displayed decreased rheobase, increased excitability as measured by firing rates to depolarizing current injections, increased inward rectification, increased input resistance, and decreased dendritic complexity compared to D1 SPNs. Our results demonstrate a dichotomy in the electrophysiological properties of D1 and D2 SPNs in the nucleus accumbens core, which contributes to our knowledge of ventral striatal circuitry.

MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core

“…To determine whether the alterations in inhibitory transmission are due to action potential dependent or independent release of neurotransmitter we also assed tetrodotoxin -insensitive mIPSCs (TTX, voltage-gated sodium channel blocker). mIPSC frequency was increased in D1 SPNs of MMP-1OE (0.95 ± 0.13 Hz) mice in comparison those from either control 29 (0.39 ± 0.08 Hz, p = 0.0102) or MMP-1OE/PAR-1KO mice (0.39 ± 0.07 Hz, p = 0.0067, Fig. 1b,g ).…”

“…sIPSC frequency was significantly increased in D1 SPNs from MMP-1OE mice (1.4 ± 0.16 Hz) in comparison to those from either control 29 (0.71 ± 0.14 Hz, p = 0.0165) or MMP-1OE/PAR-1KO mice (0.74 ± 0.13 Hz, p = 0.0219, Fig. 1a,c ).…”

“…We compared the average frequency, amplitude, rise time, and decay time of synaptic currents in D1 and D2 SPNs in control 29 , MMP-1OE mice (mice that overexpress MMP-1), and MMP-1OE/PAR-1KO mice (MMP-1OE mice that lack PAR-1). Both spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature IPSCs (mIPSCs) as well as miniature excitatory PSCs (mEPSCs) were measured to probe the source of alterations in inhibitory and excitatory currents.…”

“…Comparison of mIPSC peak amplitude ( h ), rise time ( i ), and decay time ( j ) between control, MMP-1OE, and MMP-1OE/PAR-1KO mice. The data source for controls is the same as in Al-muhtasib et al ., 2018 29 . N = control (11 cells from 7 animals), MMP-1OE (12 cells from 10 animals), and MMP-1OE/PAR-1KO (10 cells from 9 animals).…”

Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA

“…Several reports have shown that changes in neuronal excitability correlate with remodeling of their dendritic arbors (Al-Muhtasib et al, 2018;Cazorla et al, 2012;Fieblinger et al, 2018). We assessed this with Sholl analysis of three dimensional neuritic arbor reconstructions from streptavidin labeled ChIs that were filled with biotin during recording ( Figure 3A).…”