Biology subjects

Johansson, Y.

Publications and source records attributed to Johansson, Y..

3 recordsLinked to original sources

bioRxiv2023

Serotonergic and dopaminergic neurons in the dorsal raphe are differentially altered in a mouse model for Parkinson's disease.

Parkinsons disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor co-morbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both noradrenaline and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.

neuroscience↗

bioRxiv2022

Action prediction error: a value-free dopaminergic teaching signal that drives stable learning

Animals choice behavior is characterized by two main tendencies: taking actions that led to rewards and repeating past actions. Theory suggests these strategies may be reinforced by different types of dopaminergic teaching signals: reward prediction error (RPE) to reinforce value-based associations and movement-based action prediction errors to reinforce value-free repetitive associations. Here we use an auditory-discrimination task in mice to show that movement-related dopamine activity in the tail of the striatum encodes the hypothesized action prediction error signal. Causal manipulations reveal that this prediction error serves as a value-free teaching signal that supports learning by reinforcing repeated associations. Computational modeling and experiments demonstrate that action prediction errors alone cannot support reward-guided learning but when paired with the RPE circuitry they serve to consolidate stable sound-action associations in a value-free manner. Together we show that there are two types of dopaminergic prediction errors that work in tandem to support learning.

neuroscience↗

bioRxiv2021

Tonic engagement of nicotinic receptors bidirectionally controls striatal spiny projection neuron spike timing

Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can disynaptically inhibit SPNs by activating 4{beta}2 nicotinic acetylcholine receptors (nAChRs) on various GINs. Measurements of this disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that respond only weakly to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices we show that upon synchronous optogenetic activation of corticostriatal projections blockade of 4{beta}2 nAChRs shortened SPN spike latencies and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond strongly to phasic CIN activation. In particular, the observed decrease in spike latency caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, a parallel hyperpolarization of PV-FSIs, and was occluded by pharmacologically preventing cortical activation of PV-FSIs. Taken together, we describe a role for tonic (as opposed to phasic) activation of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs maintains a GABAergic brake on cortically-driven striatal output by "priming" feedforward inhibition, a process that may shape SPN spike timing, striatal processing and synaptic plasticity. Impact StatementA novel mechanism describing how tonic activation of nicotinic acetylcholine receptors can modulate the timing of striatal output by priming feed forward inhibition.

neuroscience↗