Identifying key brain circuits for learning from negative experiences

Summary: Researchers have identified brain regions and neuron types crucial for learning from negative experiences. They discovered that inhibitory neurons located in the horizontal branch of Broca's diagonal band (HDB) play an important role in this process.

Using optogenetics, they demonstrated that these neurons are essential for associative learning from aversive stimuli, highlighting their importance in attention and learning. This finding provides insight into how negative experiences shape behavior and learning.

Highlights:

1. HDB-PV neurons, located in a deep nucleus of the brain, are essential for learning from negative experiences.
2. These neurons increase cortical excitability through disinhibition, thereby facilitating associative learning.
3. Optogenetic experiments showed that blocking HDB-PV neurons impairs learning from aversive stimuli.

Source: Institute of Experimental Medicine

“I won’t do that anymore,” we often say when faced with negative feedback, side effects or disappointing results. So, we try to learn from these negative experiences.

This principle is also a cornerstone of our education system: failing an exam should motivate students to do better next time.

How does the brain achieve this type of learning? Positive and negative reinforcement appear to be two sides of the same coin in some parts of the brain's evaluation system.

Notably, some neurons that release the neuromodulator “dopamine” show better or worse outcomes than expected with an increase or decrease in their activity, respectively.

At the same time, accumulating evidence suggests that other parts of the brain handle “negative” and “positive” in fundamentally different ways.

Negative experiences, when encountered, often have an exciting effect: they leave us neither indifferent nor carefree.

Beyond this general awareness, specific parts of the neocortex are activated, allowing us to pay attention to relevant features and, eventually, draw consequences and learn – a concept sometimes called “attention for awareness.” learning “.

By focusing on the negative side of things, we can invent this “attention to aversive learning”.

A team of neuroscientists from the HUN-REN Institute of Experimental Medicine in Budapest, Hungary, led by principal investigator Balazs Hangya MD PhD, asked which brain regions and neuron types might be responsible for “attention-related to aversive learning.

In a new study published today in Natural communicationsthe team reports that long-range projecting inhibitory neurons that express parvalbumin (PV), a calcium-binding protein known for its very rapid activity capabilities, located in a deep brain nucleus called the “horizontal limb of the band Broca diagonal” or HDB plays a key role in this process.

These HDB-PV neurons have previously been shown to transmit excitatory effects to the neocortex at short and long time scales, and control rapid cortical brain waves called gamma oscillations, important for cognitive processes. Therefore, they emerged as good candidates for mediating “attention to aversive learning.”

Hangya's team showed that these neurons are indeed recruited by aversive events in experimental mice, such as an unexpected puff of air to the face that the mice strive to avoid, or the smell of a fearful predator.

Such aversive events obviously affect both humans and animals and thus activate a number of pathways causing a series of consequences in the brain.

Above all, these events can represent a chance of lasting negative impact, or even an immediate danger, the probability of which should be mitigated by avoidance behaviors. Indeed, many neural pathways recruited by aversive input have been shown to lead to active avoidance.

Second, unexpected aversive events should increase arousal and attention by activating relevant parts of the neocortex, thereby recruiting resources to cope with the situation.

Third, and crucial for long-term survival, aversive events should induce learning to avoid or reduce the impact of similar scenarios in the future.

“Learning from negative experiences is an ancient and deeply rooted survival strategy. It is so strong that we can sometimes experience it ourselves, that it can even cancel out the effect of positive reinforcement,” adds Panna Hegedüs, first author of the study.

Hangya's team used a technology called optogenetics, which can make specific cell types, in this case HDB-PV neurons, sensitive to light. These techniques enable precise activation or suppression of neuron activity by programmed delivery of light into brain tissue via small optical fibers.

They found that activation of HDB-PV neurons did not cause avoidance behavior in mice, suggesting that this pathway is not involved in active avoidance such as seeking shelter, but that it more likely mediates attention and/or aspects of learning induced by aversive stimuli.

Indeed, when optogenetically blocking neuron responses to facial air puffs, mice failed to learn discriminative predictive auditory stimuli predicting probable or improbable air puffs. This experiment demonstrated that HDB-PV neurons are necessary for learning aversive stimuli.

Which brain circuit ensures this learning effect? Neurons do not act in isolation but are part of complex circuits with various input and output pathways. Hangya's team, with Gabor Nyiri and colleagues from the same institute, mapped the inputs and outputs of HDB-PV neurons.

They found that these cells integrate multiple sources of aversive information, including important pathways from the hypothalamus and raphe nuclei of the brainstem. In turn, they transmit integrated information to the so-called limbic system, largely responsible for behavioral and emotional responses, including the septo-hippocampal system important for the storage and recall of episodic memories.

Additionally, inhibitory HDB-PV cells primarily target other inhibitory neurons in these regions, thus likely relieving excitatory cells of inhibition, allowing them to be more active – a ubiquitous brain mechanism called disinhibition.

In summary, the study suggests that long-range inhibitory HDB-PV neurons are recruited by aversive stimuli to perform crucial associative learning functions by increasing cortical excitability at specific target areas, likely through disinhibition. Thus, at least for aversive stimuli, HDB-PV neurons could be the physical substrate of the concept of “attention for learning”.

“Dysregulation of positive and negative valence processing can be observed in different psychiatric disorders, including anxiety and depression.” It is therefore crucial to understand how negative valence is encoded in the brain and how it contributes to learning,” concludes Panna Hegedüs.

About this news on learning and research in neuroscience

Author: Marta Turek
Source: Institute of Experimental Medicine
Contact: Marta Turek – Institute of Experimental Medicine
Picture: Image is credited to Neuroscience News

Original research: Free access.
“Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience” by Balazs Hangya et al. Natural communications

Abstract

Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience

Basal forebrain GABAergic neurons (BFPVNs) expressing parvalbumin (PV) have been proposed to serve as a rapid, transient arousal system, but their exact role in arousal behaviors remains unclear.

We performed global calcium measurements and electrophysiology with optogenetic labeling from the horizontal limb of Broca's diagonal band (HDB) while male mice performed an associative learning task.

BFPVN responded with distinct phasic activation to punishment, but showed slower and delayed responses to reward and outcome prediction stimuli.

Optogenetic inhibition during punishment impaired the formation of signal-outcome associations, suggesting a causal role for BFPVNs in associative learning.

BFPVNs received strong inputs from the hypothalamus, septal complex, and medial raphe region, while they synapsed on various cell types in key limbic structures, where they broadcast information about aversive stimuli.

We propose that the arousal effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions.