medium spiny neurons

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions

Understanding how macroscale brain dynamics are shaped by microscale mechanisms is crucial in neuroscience. We investigate this relationship in animal models by directly manipulating cellular properties and measuring whole-brain responses using resting-state fMRI. Specifically, we explore the impact of chemogenetically neuromodulating D1 medium spiny neurons in the dorsomedial caudate putamen (CPdm) on BOLD dynamics within a striato-thalamo-cortical circuit in mice. Our findings indicate that CPdm neuromodulation alters BOLD dynamics in thalamic subregions projecting to the dorsomedial striatum, influencing both local and inter-regional connectivity in cortical areas. This study contributes to understanding structure–function relationships in shaping inter-regional communication between subcortical and cortical levels.

Off-policy learning in the basal ganglia

I will discuss work with Jack Lindsey modeling reinforcement learning for action selection in the basal ganglia. I will argue that the presence of multiple brain regions, in addition to the basal ganglia, that contribute to motor control motivates the need for an off-policy basal ganglia learning algorithm. I will then describe a biological implementation of such an algorithm that predicts tuning of dopamine neurons to a quantity we call "action surprise," in addition to reward prediction error. In the same model, an implementation of learning from a motor efference copy also predicts a novel solution to the problem of multiplexing feedforward and efference-related striatal activity. The solution exploits the difference between D1 and D2-expressing medium spiny neurons and leads to predictions about striatal dynamics.

Dissecting the role of accumbal D1 and D2 medium spiny neurons in information encoding

Nearly all motivated behaviors require the ability to associate outcomes with specific actions and make adaptive decisions about future behavior. The nucleus accumbens (NAc) is integrally involved in these processes. The NAc is a heterogeneous population primarily composed of D1 and D2 medium spiny projection (MSN) neurons that are thought to have opposed roles in behavior, with D1 MSNs promoting reward and D2 MSNs promoting aversion. Here we examined what types of information are encoded by the D1 and D2 MSNs using optogenetics, fiber photometry, and cellular resolution calcium imaging. First, we showed that mice responded for optical self-stimulation of both cell types, suggesting D2-MSN activation is not inherently aversive. Next, we recorded population and single cell activity patterns of D1 and D2 MSNs during reinforcement as well as Pavlovian learning paradigms that allow dissociation of stimulus value, outcome, cue learning, and action. We demonstrated that D1 MSNs respond to the presence and intensity of unconditioned stimuli – regardless of value. Conversely, D2 MSNs responded to the prediction of these outcomes during specific cues. Overall, these results provide foundational evidence for the discrete aspects of information that are encoded within the NAc D1 and D2 MSN populations. These results will significantly enhance our understanding of the involvement of the NAc MSNs in learning and memory as well as how these neurons contribute to the development and maintenance of substance use disorders.

Complex interaction between postnatal acute mTOR inhibition and in utero valproic acid exposure on the morphological, functional and molecular features of accumbal medium spiny neurons

Directly reprogrammed medium spiny neurons for studying pathology and synaptic dysfunction in Huntington's disease in vitro model

An all iPSC-derived cortico-striato-nigral minicircuit modelling Parkinson’s Disease revealed electrophysiological changes in medium spiny neurons cocultured with dopaminergic neurons carrying GBA N370S mutation

Pharmacological activation of histamine receptor type 2 enhances evoked firing in medium spiny neurons of the nucleus accumbens through downregulation of Kv4.2 channels

Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons

FENS Forum 2024

Glycine modulates the excitability of medium spiny neurons in the nucleus accumbens through GPR158 activation

FENS Forum 2024

K-Cl cotransporter KCC2 function is impaired in D2 receptor-expressing medium spiny neurons in a mouse model of Huntington's disease

FENS Forum 2024