To understand the principles of operation of the striatum it is critical to elucidate the properties of the main excitatory inputs from cortex and thalamus, as well as their ability to activate the main neurons of the striatum, the medium spiny neurons (MSNs). As the thalamostriatal projection is heterogeneous, we set out to isolate and study the thalamic afferent inputs to MSNs using small localized injections of adeno-associated virus carrying fusion genes for channelrhodopsin-2 and YFP, in either the rostral or caudal regions of the intralaminar thalamic nuclei (i.e. the central lateral or parafascicular nucleus). This enabled optical activation of specific thalamic afferents combined with whole-cell, patch-clamp recordings of MSNs and electrical stimulation of cortical afferents, in adult mice. We found that thalamostriatal synapses differ significantly in their peak amplitude responses, short-term dynamics and expression of ionotropic glutamate receptor subtypes. Our results suggest that central lateral synapses are most efficient in driving MSNs to depolarization, particularly those of the direct pathway, as they exhibit large amplitude responses, short-term facilitation and predominantly express postsynaptic AMPA receptors. In contrast, parafascicular synapses exhibit small amplitude responses, short-term depression and predominantly express postsynaptic NMDA receptors, suggesting a modulatory role, e.g. facilitating Ca2+-dependent processes. Indeed, pairing parafascicular, but not central lateral, presynaptic stimulation with action potentials in MSNs, leads to NMDA receptor- and Ca2+-dependent long-term depression at these synapses. We conclude that the main excitatory thalamostriatal afferents differ in many of their characteristics and suggest that they each contribute differentially to striatal information processing.
Many electronic devices that we use in our daily lives provide inputs that need to be processed and integrated by our senses. For instance, ringing, vibrating, and flashing indicate incoming calls and messages in smartphones. Whether the presentation of multiple smartphone stimuli simultaneously provides an advantage over the processing of the same stimuli presented in isolation has not yet been investigated. In this behavioral study we examined multisensory processing between visual (V), tactile (T), and auditory (A) stimuli produced by a smartphone. Unisensory V, T, and A stimuli as well as VA, AT, VT, and trisensory VAT stimuli were presented in random order. Participants responded to any stimulus appearance by touching the smartphone screen using the stimulated hand (Experiment 1), or the non-stimulated hand (Experiment 2). We examined violations of the race model to test whether shorter response times to multisensory stimuli exceed probability summations of unisensory stimuli. Significant violations of the race model, indicative of multisensory processing, were found for VA stimuli in both experiments and for VT stimuli in Experiment 1. Across participants, the strength of this effect was not associated with prior learning experience and daily use of smartphones. This indicates that this integration effect, similar to what has been previously reported for the integration of semantically meaningless stimuli, could involve bottom-up driven multisensory processes. Our study demonstrates for the first time that multisensory processing of smartphone stimuli facilitates taking a call. Thus, research on multisensory integration should be taken into consideration when designing electronic devices such as smartphones.
Our results are consistent with an ability of acute, low-dose pramipexole to diminish dopamine-mediated responses to both rewarding and aversive taste stimuli, perhaps through an inhibitory action of D2/3 autoreceptors on phasic burst activity of midbrain dopamine neurones. The ability of pramipexole to inhibit aversive processing might potentiate its adverse behavioural effects and could also play a role in its proposed efficacy in treatment-resistant depression.
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