Dopamine neuron glutamate cotransmission evokes a delayed excitation in lateral dorsal striatal cholinergic interneurons

Abstract

Dopamine neurons have different synaptic actions in the ventral and dorsal striatum (dStr), but whether this heterogeneity extends to dStr subregions has not been addressed. We have found that optogenetic activation of dStr dopamine neuron terminals in mouse brain slices pauses the firing of cholinergic interneurons in both the medial and lateral subregions, while in the lateral subregion the pause is shorter due to a subsequent excitation. This excitation is mediated mainly by metabotropic glutamate receptor 1 (mGluR1) and partially by dopamine D1-like receptors coupled to transient receptor potential channel 3 and 7. DA neurons do not signal to spiny projection neurons in the medial dStr, while they elicit ionotropic glutamate responses in the lateral dStr. The DA neurons mediating these excitatory signals are in the substantia nigra (SN). Thus, SN dopamine neurons engage different receptors in different postsynaptic neurons in different dStr subregions to convey strikingly different signals.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum

“…It is known that dopamine alters the input resistance of MSNs in vivo (Ketzef et al, 2017). Therefore, distinct dopaminergic innervation of the DLS-and DMS-MSNs (Chuhma et al, 2018) could underlie our differences in resistance between striatal regions.…”

“…Under anaesthesia, dopaminergic neurons of the Substantia Nigra discharge spontaneous action potentials, in tonic or burst firing mode (Aristieta et al, 2016;Brown et al, 2009). This dopaminergic activity could induce different effects on the SWO in DLS-and DMS-MSNs, either directly mediated by distinct dopaminergic projections (Brown et al, 2009) or indirectly by their varied impact on ChIs activity along the mediolateral axis (Chuhma et al, 2018). Finally, it has been recently shown that SOM corticostriatal interneurons modulate the MSNs activity from motor cortical areas (Melzer et al, 2017;Rock et al, 2016).…”

“…The distribution of parvalbumin (PV) and cholinergic interneurons (ChIs) along the mediolateral axis of the DS is not homogeneous (Gerfen et al, 1985;Kita et al, 1990;Matamales et al, 2016;Muñoz-Manchado et al, 2018). Furthermore, dopaminergic projections from the lateral part of the substantia nigra massively innervate the DS (Ikemoto, 2007), with particular impact in the activity of ChIs along the DS (Chuhma et al, 2018). All these precise afferent connectivity, microcircuit interactions and neuromodulation regulate the synaptic activity of DLS-and DMS-MSNs.…”

It takes two to tango: Dorsal direct and indirect pathways orchestration of motor learning and behavioral flexibility

“…Midbrain DA neurons are heterogeneous not only regarding their axonal projections but also their morphological (e.g. variable dendrite architecture), molecular (GABA and glutamate co-release) and electrophysiological properties (Wolfart et al, 2001;Neuhoff et al, 2002;Amendola et al, 2012;Tritsch and Sabatini, 2012;Henny et al, 2012;Chuhma et al, 2018). In addition, DA neurons can be excited by both rewarding and aversive stimuli, suggesting that DA neurons participate in distinct circuits mediating partially distinct functions (Lammel et al, 2014;Morales and Margolis, 2017) As previously mentioned, behavioral flexibility is mediated by prefrontal connections to the striatum.…”

In vivo functional diversity of midbrain dopamine neurons within identified axonal projections

“…The functional properties and the emerging diversity of the midbrain dopamine (DA) system have been extensively studied across many different biological scales (Schultz, 2015;Watabe-Uchida et al, 2017). These differences range from the single-cell level, including diverging gene expression profiles (Kramer et al, 2018;Nichterwitz et al, 2016;Poulin et al, 2018;Saunders et al, 2018a;Tiklova et al, 2019), cellular and biophysical properties Lammel et al, 2008;Tarfa et al, 2017), as well as neurotransmitter co-release (Chuhma et al, 2018;Kim et al, 2015b;Tritsch et al, 2012;Zhang et al, 2015), up to different neural circuit affiliations (Beier et al, 2019;Beier et al, 2015;Lammel et al, 2012;Lerner et al, 2015;Menegas et al, 2015;Ogawa et al, 2014;Tian et al, 2016;Watabe-Uchida et al, 2012) and selective task engagement of DA subpopulations in awake behaving rodents (Dautan et al, 2016;de Jong et al, 2019;Duvarci et al, 2018;Gunaydin et al, 2014;Howe and Dombeck, 2016;Keiflin et al, 2019;Lammel et al, 2012;Matthews et al, 2016;Menegas et al, 2018;Menegas et al, 2017;Parker et al, 2016;Patriarchi et al, 2018;Saunders et al, 2018b;Vander Weele et al, 2018;Yang et al, 2018) and non-human primates …”