Chemical Interactions with Pyramidal Neurons in Layer 5 of the Cerebral Cortex: Control of Pain and Anxiety

Pyramidal neurons in layer 5 of the cerebral cortex, crucial for learning and memory, have dendrites that can switch between long-term depression and potentiation based on summed inputs from many interneurons and distant neurons. Serotonin is a key neurotransmitter involved with these neurons and has been linked to psychosis, psychedelic states, and sacred dreams. This review discusses chemicals and receptors important for pyramidal neurons, including opioids, nicotine, scopolamine, psilocybin, LSD, mescaline, ergot alkaloids, salvinorin A, and ergine, which interact with opioid, nicotinic, muscarinic, and serotonergic receptors. It proposes that each receptor has a natural agonist and antagonist, often peptides, and suggests possible peptide structures for these, offering new avenues for exploring pyramidal neuron functions in health and pain management.

Study at a glance

Abstract

Pyramidal neurons in layer 5 of the cerebral cortex are involved in learning and memory and have complex connections with other neurons through a very large array of dendrites. These dendrites can switch between long term depression and long term potentiation depending on global summation of various inputs. The plasticity of the input into pyramidal neurons makes the neuronal output variable. Many interneurons in the cerebral cortex and distant neurons in other brain regions are involved in providing input to pyramidal neurons. All of these neurons and interneurons have neurotransmitters that act through receptors to provide input to pyramidal neurons. Serotonin is one of the important neurotransmitters involved with pyramidal neurons and has been implicated in psychosis, psychedelic states and what are called sacred dreams. This review will discuss the various chemicals and receptors that are important with pyramidal neurons including opioids, nicotine, scopolamine, psilocybin, LSD, mescaline, ergot alkaloids, salvinorin A, ergine and other compounds that interact with opioid, nicotinic, muscarinic and serotonergic receptors. The natural compounds provide clues to structure activity relationships with the receptors. It has been postulated that each receptor in the body has a natural agonist and antagonist, in addition to the normal neurotransmitters. It is common for natural antagonists and agonists to be peptides. Various possible peptide structures will be proposed for natural antagonists and agonists at each receptor. Natural antagonists and agonists may provide new ways to explore the functions of pyramidal neurons in normal health and pain management.