Oxytocin: decreasing cacophony in the brain
Ah oxytocin, somehow I just can’t seem to escape you. The media darling “love” (or not) hormone is back in the news, but in a slightly different way. Previous reports often focus on how it influences behaviour. Now a new paper is offering us an enthralling answer to a more basic but crucial question: in terms of neurophysiology, what the hell is it doing in the brain?
Scott F Owen et al (2013) Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature doi:10.1038/nature12330
Insert oxytocin primer: it is a hormone-neurotransmitter released from a part of the brain called the hypothalamus. As a hormone, it circulates the body and promotes child birth; as a neurotransmitter, it acts on many different parts of the brain by binding to its receptor, and is linked to intimacy, mate bonding, facial recognition, social interaction and –on the flip side – anxiety and fear. It’s a truly “dirty” aka non-specific drug.
A key clue stems from a 30-year-old finding, in which researchers found that oxytocin increases inhibitory signalling in the hippocampus, a brain region important in aspects of learning and memory. These inhibitory neurons release GABA, a neurotransmitter that dampens the activity of nearby excitatory pyramidal cells. How this relates to oxytocin’s ability to improve information processing in the brain on the circuit level was left unexplored.
To tackle this question, researchers eavesdropped on the electrical chattering in neurons residing in a small part of the hippocampus called CA1. Using electrophysiology to measure electrical activity in neurons, they specifically looked at the flow of information through this region. As shown in the graph below, when researchers used tiny electrodes to stimulate axons called Schaffer Collaterals (“wires” through which electrical signals/information travels) leading to CA1 neurons, it activates both excitatory pyramidal cells (blue) and adjacent small inhibitory cells (purple and green), the latter of which synapses onto pyramidal cells (blue) to lower their excitation.
Due to their membrane properties, many neurons are inherently “noisy”, often spontaneously firing without external stimuli. Picking out actual information then is like trying to chat with a specific person at a crowded cocktail party: the signal (the other person’s voice) needs to be strong, and the background noise weak. Researchers first used a microelectrode to zap axons leading to CA1 to create artificial “information” (the black spike diagramed above).
As you can see from the left graph above, when they concurrently used an oxytocin-like molecule (TGOT) to stimulate oxytocin receptors, excitatory neurons had a much higher probability of transferring the signal (the spike) to the next neuron in a more timely fashion (compare TGOT to baseline, spike probability is increased). In other words, it's as if the neuron became a better relayer, so that its downstream receiver had a higher chance of getting the information, increasing fidelity.
On the contrary, as shown in the right graph, spontaneous activity (baseline spikes) of these excitatory neurons decreased. On the circuit level, this is like turning on noise-cancelling headphones: things that you want to hear become clearer, while ambient chatter fades away.
How is this happening? Using various chemical blockers and electrophysiology, researchers found more and stronger spontaneous firing in a type of inhibitory neurons called Fast-Spiking Interneurons. This increases overall inhibitory tone in the circuit, which may partially account for a decrease in random background noise.
But if inhibitory neurons are firing MORE after oxytocin, shouldn't they also inhibit the signal that's getting passed along in pyramidal cells? Nope. Fast-Spiking Interneurons can fire either spontaneously or when information flows through (called "evoked"). With a bit more electrophysiology sleuthing, researchers found that although oxytocin increased spontaneous firing of these interneurons, it actually decreased information-stimulated/evoked firing. Since interneurons synapse onto neighbouring excitatory cells, this results in less inhibition of the excitatory cells and a stronger signal.
The TLDR then, is that oxytocin strengthens information transfer and decreases spontaneous background noise in the hippocampus. Okay, so what? This sharpening of information processing in brain circuits may go awry in conditions like autism. Previous research has found that children with autism have lower oxytocin levels in the bloodstream, and in some cases, mutations in the oxytocin receptor. Lower oxytocin could result in poorer signal/noise processing. Although this study links oxytocin signalling to circuit difficulties, the jury is still out there about its potential therapeutic implications, if any.
Beyond autism, oxytocin is hypothesized to increase saliency of social interactions in the “neurotypical” as well. That is, it focuses our attention to different contexts and cues, making them more noteworthy. While a long stretch, it’s still intriguing to wonder if oxytocin’s enhancement of signal-to-noise ratio may underlie this “spotlight” effect. If so, those with autism may find social interactions nerve wracking because - on the circuitry level - they can’t separate pertinent signals from all the background cacophony.
Owen SF, Tuncdemir SN, Bader PL, Tirko NN, Fishell G, & Tsien RW (2013). Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature PMID: 23913275