Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN) in awake, behaving rats evokes distinct local field potential (LFP) responses (onset latency ~13 ms) in the prelimbic (PrL) subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5–10 Hz). Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.
Synaptogenesis and the role of dendritic protrusions in this process are well studied in glutamatergic synapses. Much less is known about the formation of GABAergic synapses, which are located predominantly on the dendritic shaft. We used genetically labeled interneurons in mature hippocampal slice cultures and two-photon laser-scanning microscopy to examine contact formation between GABAergic axons and the dendrites of CA1 pyramidal cells. Dendritic protrusions distinguished and selected between glutamatergic and GABAergic boutons. In contrast with contacts with glutamatergic boutons, which can be long lasting, the contacts of dendritic protrusions with GABAergic boutons were always short lived. Similarly, the contacts made by GABAergic axonal protrusions were always transient. New putative GABAergic synapses were formed exclusively by new boutons appearing at pre-existing axon-dendrite crossings without the involvement of any dendritic or axonal protrusions. These findings imply that fundamentally different mechanisms underlie the generation of GABAergic and glutamatergic synapses.
Activity-dependent changes in the synaptic connections of the brain are thought to be important for learning and memory. Imaging techniques have enabled the examination of structural rearrangements during activity-dependent processes at the synapse. While many studies have examined structural changes of dendritic spines, little is known about structural plasticity of presynaptic boutons. We therefore examined how axonal boutons are affected during long-term depression (LTD). We used time lapse two-photon laser scanning microscopy and extracellular field recordings to monitor simultaneously synaptic morphology and activity for up to five hours in mouse organotypic hippocampal slice cultures. LTD induction dramatically increased the turnover of presynaptic boutons, while decreasing the number of putative synaptic contacts between Schaffer collateral boutons and spines of CA1 pyramidal cells. Our data indicate a substantial presynaptic contribution to activity-dependent morphological plasticity and provide opportunities for studying the molecular mechanisms of the structural remodeling of synaptic circuits.
The learning processes underlying the formation of drug-cue associations involve changes in synaptic transmission mediated by AMPA receptors. Here, we examine the consequences of targeted deletion of the gene encoding GluR1 subunits of AMPA receptors (gria1 knockouts (KO)) on cocaine self-administration and on the ability of cocaine-paired cues to affect cocaine-seeking in mice. Cocaine selfadministration was unaffected by gria1 deletion, as was the ability of a cocaine-paired cue to reinstate responding following extinction, following either a 3 or a 66 day delay. However, gria1 KOs over-responded during extinction. The KOs were unable initially to learn a new response to access a cue previously conditioned to cocaine (conditioned reinforcement (CR)), although a second test 2 months later revealed that this was a transient deficit. These studies indicate that GluR1-containing AMPA-receptors are not involved in cocaine self-administration, cue-induced reinstatement of cocaine seeking, or incubation of the cocaine seeking response. In order to understand the specificity of the deficits in CR responding, a parallel study was performed with food reward. As with cocaine, there were no effects of gria1 deletion on food self-administration or cue-induced reinstatement, and KOs over-responded during extinction. However, even immediately after instrumental training for food, KO mice demonstrated responding for CR, suggesting that the CR deficit observed with a cocaine cue is specific to drug reward. These data indicate that GluR1-containing AMPA receptors are important in stimulus reward learning, though the method of cue-reward association formation, the reward class, and the behavioral end point are critical variables in determining their involvement.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.