Continuous representations of speed by striatal medium spiny neurons

The striatum is critical for controlling motor output. However, it remains unclear how striatal output neurons encode and facilitate movement. A prominent theory suggests that striatal units encode movements in bursts of activity near specific events, such as the start or end of actions. These bursts are theorized to gate or permit specific motor actions, thereby encoding and facilitating complex sequences of actions. An alternative theory has suggested that striatal neurons encode continuous changes in sensory or motor information with graded changes in firing rate. Supporting this theory, many striatal neurons exhibit such graded changes without bursting near specific actions. Here, we evaluated these two theories in the same recordings of mice (both male and female). We recorded single-unit and multiunit activity from the dorsomedial striatum of mice as they spontaneously explored an arena. We observed both types of encoding, although continuous encoding was more prevalent than bursting near movement initiation or termination. The majority of recorded units did not exhibit positive linear relationships with speed but instead exhibited nonlinear relationships that peaked at a range of locomotor speeds. Bulk calcium recordings of identified direct and indirect pathway neurons revealed similar speed tuning profiles, indicating that the heterogeneity in response profiles was not due to this genetic distinction. We conclude that continuous encoding of speed is a central component of movement encoding in the striatum

An open-source device for measuring food intake and operant behavior in rodent home-cages

Feeding is critical for survival, and disruption in the mechanisms that govern food intake underlies disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation in rodent home-cages: the Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs

Data from: Altered development of synapse structure and function in striatum caused by Parkinson's disease-linked LRRK2-G2019S mutation

Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) can cause Parkinson's disease (PD), and the most common disease-associated mutation, G2019S, increases kinase activity. Because LRRK2 expression levels rise during synaptogenesis and are highest in dorsal striatal spiny projection neurons (SPNs), we tested the hypothesis that the LRRK2–G2019S mutation would alter development of excitatory synaptic networks in dorsal striatum. To circumvent experimental confounds associated with LRRK2 overexpression, we used mice expressing LRRK2–G2019S or D2017A (kinase-dead) knockin mutations. In whole-cell recordings, G2019S SPNs exhibited a fourfold increase in sEPSC frequency compared with wild-type SPNs in postnatal day 21 mice. Such heightened neural activity was increased similarly in direct- and indirect-pathway SPNs, and action potential-dependent activity was particularly elevated. Excitatory synaptic activity in D2017A SPNs was similar to wild type, indicating a selective effect of G2019S. Acute exposure to LRRK2 kinase inhibitors normalized activity, supporting that excessive neural activity in G2019S SPNs is mediated directly and is kinase dependent. Although dendritic arborization and densities of excitatory presynaptic terminals and postsynaptic dendritic spines in G2019S SPNs were similar to wild type, G2019S SPNs displayed larger spines that were matched functionally by a shift toward larger postsynaptic response amplitudes. Acutely isolating striatum from overlying neocortex normalized sEPSC frequency in G2019S mutants, supporting that abnormal corticostriatal activity is involved. These findings indicate that the G2019S mutation imparts a gain-of-abnormal function to SPN activity and morphology during a stage of development when activity can permanently modify circuit structure and function

Stats_Matikainen Ankney _Kezunovic et al

Summary table of all statistics used. Means and n's are provided in the associated paper