A Crash Course In Neuron Activation

In this article, we will take a close look at the process of neuron activation, particularly relating to action potentials. We will understand the role of neurotransmitters and neuromodulators in neuron activation, and discuss the innovative methods like optogenetics and chemogenetics used in labs to activate neurons. We will also explore the critical role of neuron activation in our daily activities such as movement, vision, hearing, and thinking.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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What is Neuron Activation?

Neuron activation occurs when a neuron reaches its hyperpolarisation threshold through a combination of electrical input and its accumulation within the cell body. Another word for neuron activation is an action potential - an impulse that is generated at one end of a neuron and transmitted down the axon to a proximal or distal target [1, 2].

The action potential is propagated thanks to sodium channels, which open in response to a shift in the electrochemical gradient that the neuron activation generates [3].

An action potential is a rapid sequence of changes in the voltage across a cell membrane, primarily driven by the opening and closing of ion channels. The process begins with a change in sodium channel permeability, causing sodium ions to rush into the cell, a process known as depolarization. This action potential spreads to adjacent sections of the axon, creating an electrochemical wave 1. The subsequent return to resting potential, repolarization, is mediated by the opening of potassium ion channels. An ATP-driven pump (Na/K-ATPase) then reestablishes the balance of ions by moving sodium ions out of the cell and potassium ions into the cell 2. This process is a dissipative one, producing entropy and using free energy, and it involves an exogenous energy source, as the energy dissipated by the ionic flows or the applied stimulus depolarization are far too small to account for the overall energy balance 3.

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In the human brain, neurons are activated by neurotransmitters and neuromodulators, such as glutamate, GABA, glycine, dopamine, serotonin and norepinephrine [4]. These neurotransmitters are released from the synaptic cleft of one neuron and can open specific channels or activate receptors on the second neuron. This generates the electrochemical gradient that propels the action potential along the axon. Co-occuring neural activation is also important for synaptic plasticity and learning.

In the lab, neuron activation can be achieved in animals, such as mice or monkeys, and neuron activation can be achieved in a living organism or in a dish [5]. One way is to supply a steady electrical current, called a ‘square pulse’, which can depolarize the cell (make it less negative), and hence likely to fire an action potential. One can also supply bursts of electrical current, accumulating towards depolarising the neuron towards neuron activation [6].

In recent years, more elaborate ways to activate neurons have been developed. These include cell-specific activation methods, including optogenetics and chemogenetics. Let’s have a look at these two methods in more detail.

Side note

Deep neural networks were inspired by living neural networks but work on different principles.

Neuron Activation by Optogenetics

Optogenetics is when a genetic vector is inserted only into a specific subset of cells, such as cells in the hypothalamus expressing GLP-1 receptors. This genetic vector makes the cells sensitive to light – once you shine a specific light wavelength into this brain area, the neurons that have this vector will be activated.

Neuron Activation by Chemogenetics

Chemogenetics works very similarly to optogenetics. The most common subtype of chemogenetics is called Designer Receptors Exclusively Activated by Designer Drugs (DREADS), where a genetic viral vector is sent to specific cell types. The cells will express a specific ‘designer’ receptor, which can be activated by a substance called DMSO. Subsequently, the experimental animal will be given a meal containing DMSO, which will activate the cells or neurons targeted by the vector [6].

Importance of Neuron Activation

Activating neurons is critical to brain activity, movement and reflexes. Here is a closer discussion of how neuron activation contributes to activities of daily living:

  • Movement: When you wish to contract a muscle, the neurons in your motor cortex will send a signal down to your muscle via the basal ganglia. Once the neural impulse reaches the muscle, it will trigger a release of calcium within the muscle, initiating contraction [7].
  • Vision: Light is perceived through photoreceptors at the back of the eyeball. These receptors activate neurons that transmit the image to your occipital lobe, the hind part of the brain responsible for vision. Neuron activation within the occipital lobe orchestrates the image into a form that you are familiar with [8].
  • Hearing: Similarly to vision, sound waves from an auditory stimulus hit the inner ear organs, which activate specific neurons based on the frequency and amplitude of the sound wave. These neurons then correspond to the pitch and volume of the sound in a neural code—a specific pattern of neurons firing [9].
  • Thinking: The neural processes underlying thinking are generally not very well understood. However, when you think about a specific object, such as a face or a house, particular brain areas (such as subsets of the occipital lobe) will become more active, as demonstrated in this review by Epstein et al., in 2006 using fMRI and EEG [10]. This indicates that these neurons are activated.

Summary: Neuron Activation

To summarise, neuron activation is a complex physical process where an action potential is generated from the accumulation of charge within a neuron and an electrochemical gradient. When activated, a neuron sends an action potential down its axon, which can convey a message. There are different ways to activate neurons in the lab. This has enabled researchers to determine the importance of neuron activation in movement, vision, hearing and thinking, amongst other critical functions.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.