University:
Boston University
Course:
CAS BI 108 | Biology 2
Academic year:

2022
Views:

137

Pages:

1
Author:

Jarrett Richard

Modeling the Effect of CBD on ɑ-7 Nicotinic Acetylcholine Receptors and Firing Rates of a Cerebellar Nuclear Neuron Introduction Results ● Cannabidiol (CBD) is a chemical compound found in the cannabis sativa plant. Studies have shown that CBD may have uses in treating a variety of health problems, including anxiety, chronic pain, and insomnia. New evidence suggests that CBD may be able to help reduce seizures and treat childhood epilepsy, among other conditions. acetylcholine receptors ● Nicotinic (nAChRs) are located in the central nervous system. When acetylcholine (endogenous agonist) or nicotine (exogenous agonist) binds to nAChRs, ion channels open, allowing sodium, potassium, and calcium ions to pass through the cell membrane. Figure 2: Cerebellar nuclear neuron membrane potential - high gain. a) Baseline b) ACh c) ACh + CBD Figure 1: Diagram of a nAChR in the cell membrane. Figure 3: Number of spikes in 1000 ms for baseline, ACh, and ACh + CBD simulations. a) Low gain b) Medium gain c) High gain ● Past research has examined both the effect of CBD on ɑ-7 nicotinic acetylcholine receptors in the hippocampus and the role of nAChRs in the cerebellum. We reproduced these methods in a cerebellar nuclear neuron to investigate the effect of CBD in the cerebellum. Methods Our model was adapted in NEURON from Sudhakar et al, 2015. We first ran a baseline model of a cerebellar nuclear neuron as it receives low, medium, and high levels of input from a Purkinje cell. We made two assumptions regarding the model. ɑ-3 and ɑ-4 nAChRs have been found in the cerebellum, but the presence of ɑ-7 nAChRs in the cerebellum has not been confirmed (Turner et al). We made the assumption that CBD has a similar effect on nAChRs regardless of subtype. We permanently changed the gamma-Aminobutyric (GABA) synapse conductance value. Realistically, the cholinergic system is not active at all times. We made the assumption that our results only apply when the cholinergic system is active. ACh has been shown to increase the amount of GABA channels open. To simulate the presence of an ACh receptor, we edited the GABA synapse conductance to 120% of its original value (Turner et al). Finally, we set the synaptic conductance parameter to 60% of the 120% (72%) to simulate the addition of CBD during neuromodulation (Mahgoub et al). Discussion/ Conclusions ● The presence of ACh increases the amount of GABA channels open. Since GABA is an inhibitory neurotransmitter, this resulted in a decreased firing rate. ● Once we added the CBD, the firing rate increased. CBD inhibits ACh receptors, which in turn decreased the number of GABA receptors open and increased the neuron firing rate. This suggests that nAChRs impact cerebellar activity and circuitry when the cholinergic system is active. ● Since the disruption of normal cerebellar activity contributes to disorders involving the cerebellum, nAChRs in the cerebellum may have implications in pathological conditions, such as autism spectrum disorders (ASD). ● Further experiments can be done to test the potential effects of CBD use to address ASD and other cerebellum-related disorders. ● This model could be adapted to reflect the presence of an ɑ-3 or ɑ-4 acetylcholine receptor, which are known to be found in the cerebellum.