The code provided is a computational model designed to simulate neural activity within a thalamocortical (TC) and reticular (RE) network under the influence of the anesthetic drug propofol. The focus is on understanding how propofol affects the phenomenon known as phase-amplitude coupling (PAC), particularly in the thalamus. ### Biological Basis #### Thalamus and Reticular Nucleus - **Thalamus (TC):** The thalamus is crucial for regulating sensory and motor signals and is involved in consciousness and sleep. It forms thalamocortical relay (TC) neurons. - **Reticular Nucleus (RE):** This nucleus is part of the thalamic reticular formation and plays a key role in modulating thalamocortical rhythms. It consists mainly of GABAergic neurons that provide inhibitory feedback to the thalamus. #### Modulation by Propofol Propofol is an anesthetic known to affect synaptic transmission and neural excitability. It enhances inhibitory neurotransmission through GABA_A receptors, contributing to its anesthetic properties. This model investigates the effect of propofol on neural oscillations and phase-amplitude coupling (PAC) in the thalamus. ### Model Components 1. **Ion Channels and Ion Currents:** - **Sodium (iNa), Potassium (iK), and Leak Currents (iLeak):** Essential for action potential generation and baseline membrane properties. - **T-type Calcium Channels (iT):** Important for generating low-threshold calcium spikes, contributing to thalamic bursting behavior. - **H-current (iH):** This mixed cation current is involved in setting resting membrane potential and regulating rhythmic activities. 2. **Synaptic Mechanisms:** - **AMPA Receptors (iAMPA):** Mediate fast excitatory synaptic transmission. - **GABA_A and GABA_B Receptors (iGABAA, iGABAB):** Mediate fast and slow inhibitory synaptic transmission, respectively, enhancing inhibition in the presence of propofol. 3. **Parameters and Conditions:** - **Simulated Conditions:** The model uses variations in synaptic and intrinsic properties to simulate different neural states, comparing baseline to high-dose propofol conditions. - **Depolarized State and GH Conductance:** Parameters are varied to understand depolarization and oscillation under propofol influence. - **Designed Experiments:** Alter parameters like synaptic gain (gH), applied current (Iapp), and modulatory effects (spm) to simulate and analyze specific scenarios. ### Outcomes and Investigation Goals The goal of this modeling effort is to illustrate and investigate the effects of propofol on thalamic oscillatory activity and PAC, explaining clinical observations of altered brain rhythms under anesthesia. The model attempts to reproduce key features of thalamic behavior under drug influence at varying doses, providing insights into the neural mechanisms behind propofol's efficacy and its influence on rhythm generation within the thalamic network. This work potentially contributes to understanding how propofol alters consciousness by modifying thalamic and reticular interactions.