Browsing by Subject "Interneurons"

Now showing 1 - 2 of 2

Cholinergic interneurons and synaptic reorganization within the nucleus accumbens shell and core: potential neural substrates underlying drug addiction
(2006) Berlanga, Monica Lisa; Alcantara, Adriana A.
Drug abuse and dependence are among the most challenging public health issues facing America today. The acute treatment of drugs of abuse such as psychostimulants (Trantham-Davidson and Lavin, 2004) and opiates (Harris and Williams, 1991) produce transient changes in cellular activity and synaptic signaling. Repeated drug treatment, however, results in persistent cellular and behavioral changes, such as altered dendritic morphology and behavioral sensitization (Robinson and Kolb, 1999b). Synaptic changes in the brain are posited to underlie a repertoire of drug-induced persistent behaviors, including sensitization, psychosis and relapse. Direct evidence of drug-induced synaptic plasticity, however, has not been demonstrated. The present studies were designed to examine cholinergic neurons and synaptic rewiring as potential neural substrates involved in acute and chronic drug exposure. The proposed studies tested the hypotheses that 1) cholinergic interneurons within the nucleus accumbens (NAcc) are activated by the acute self-administration of cocaine, 2) dopamine (DA) D5 and D2 receptors localized on cholinergic interneurons potentially undergo cocaine-induced neuroadaptation, and 3) repeated administration of cocaine leads to an increase, while repeated administration of morphine leads to a decrease, in the number of synapses within the NAcc, whereas an increase in the number of synapses occurs in the NAcc core of animals exhibiting behavioral sensitization. These studies revealed that accumbal cholinergic interneurons are activated by acute cocaine self-administration and elucidate the specific localization of DA receptor subtypes, D5 and D2, on these cells, suggesting their potential role in mediating druginduced DA changes within the NAcc. The final study provided the first ultrastructural evidence that an increase in the number of excitatory synapses in the NAcc shell occurs following 4-weeks of cocaine and morphine treatment followed by 3 weeks abstinence and that cocaine sensitization is associated with an increase in the number of excitatory synapses in the NAcc core. These findings provide the groundwork for future studies examining the precise cellular and synaptic substrates underlying a repertoire of druginduced behaviors that contribute to the persistence of addiction. Improved pharmacotherapeutic and behavioral treatments can then target the specific cellular and synaptic microcircuitry critically involved in the different stages of drug abuse and dependence.
In vitro microfluidic platform for co-culture of myocytes with mouse embryonic stem cell-derived interneurons and motor neurons
(2022-12-01) Lee, Jaewon; Sakiyama-Elbert, Shelly E.; Brock, Amy; Noble, Linda; Zoldan, Janeta
Central pattern generators (CPGs) in the spinal cord are motor circuits that oversee controlling rhythmic motor activities. CPGs are composed of different types of interneurons (INs) that interact with the motor neurons (MNs) to produce the patterns of MN activity that can coordinate limb and body movements. Elucidating how different populations of INs contribute to the spinal CPG circuitry in different ways is crucial to understanding neural circuit formation and function. In addition, to study how neural circuits, such as CPGs recruit muscle and dictate locomotion, a functional neuromuscular junction (NMJ) model is essential. As CPG and NMJ are both important components in understanding spinal locomotion, a cell-culture based model where it is possible to precisely modulate cellular, molecular, or transcriptional cues in well-defined time and space is highly desirable. In this study, an in vitro NMJ and a V2a IN-MN-myotube (MT) circuit were developed as model platforms to study CPGs using the unique cell lines developed previously in the lab: transgenic mouse embryonic stem cell (mESC) lines that can produce enriched cultures of Hb9⁺ MNs and excitatory Chx10⁺ V2a INs. We established and confirmed a co-culture condition for the formation of NMJ between the unique mESC-derived Hb9⁺ MNs and the C2C12-derived myotubes in vitro and qualitatively and quantitatively assessed the functional connection between the two cell types. Our platform was further advanced to include a model IN population, Chx10⁺ V2a INs to develop a platform that allows for the characterization of IN-MN connections in situ. The in vitro circuit was made by co-culturing V2a INs, MNs, and MTs in separate chambers of the microdevice that are connected with the microchannels. A co-culture protocol for all three cell types was established using different seeding strategies and medium combinations. To evaluate the possible network formation in the dissociated cultures of different cell types, microelectrode arrays (MEAs) were used. Utilizing the techniques developed in this project, a more systematic study of rhythm and pattern generation according to the IN composition can be carried out to further elucidate the role of each IN population in circuit formation and function