Abstract
Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes. We propose that there must be a time before which stimuli cannot be processed into functional connections, otherwise it would imply an effective link between stimulus, response, and reward in uterus. Consistent with these ideas, we present evidence that early in development dopamine neurons are electrically immature and do not produce high-frequency firing in response to salient stimuli. We ask first, what makes dopamine neurons immature? and second, what are the implications of this immaturity for the basal ganglia? As an answer to the first question, we find that at birth the outward current is small (3nS-V), insensitive to , TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to , TEA, BK, and SK blockers. We make a detailed analysis of the kinetics of the components of the outward currents and produce a model for BK and SK channels that we use to reproduce the outward current, and to infer the geometrical arrangement of BK and channels in clusters. In the first cluster, T-type and BK channels are coupled within distances of 20 nm (200 Å). The second cluster consists of L-type and BK channels that are spread over distances of at least 60 nm. As for the second question, we propose that early in development, the mechanism of action selection is in a “locked-in” state that would prevent dopamine neurons from reinforcing cortico-striatal synapses that do not have a functional experiential-based value.
Highlights
The physiology of dopamine neurons of the substantia nigra (SN) has received a great deal of attention throughout the years [1] due to the role these neurons play in the regulation of the basal ganglia (BG)
A classical theoretical framework that has shaped our understanding of the function of the BG is the notion that massive parallel signals that originate in the cortex are processed by the direct and indirect pathways of the BG that arise in the striatum and constitute the beginning of a formidable feedback loop that will eventually return to the cortex via the thalamus [2,3,4,5,6]
Of 135 neurons recorded, 29 neurons were injected with Lucifer Yellow (LFY) and double labeled with TH
Summary
The physiology of dopamine neurons of the substantia nigra (SN) has received a great deal of attention throughout the years [1] due to the role these neurons play in the regulation of the basal ganglia (BG). A classical theoretical framework that has shaped our understanding of the function of the BG is the notion that massive parallel signals that originate in the cortex are processed by the direct and indirect pathways of the BG that arise in the striatum and constitute the beginning of a formidable feedback loop that will eventually return to the cortex via the thalamus [2,3,4,5,6] This classical model is very useful as a theoretical framework, it is appreciated that the the direct-indirect model needs to be complemented with several lateral and reciprocal connections that give rise to topographically organized microcircuits that process emotional, associative, sensory, and motor information [6]. Given that SN DA neurons are subject to a powerful synaptic drive, it is probable that these neurons respond with bursting to the complex interplay between excitatory synaptic input and a GABAA-dependent disinhibition mechanism [12,17,21,22,23,24]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
