Studies emphasize the importance of sensory connections in fear learning

Has your mind started competing with the impending deadline for work? Or have you ever jumped to see an unknown object in a dark room? Well, you can probably thank your amygdala for that.

The structure of the small almond-shaped brain is central to the way we recognize and process fear. As we begin to learn to associate fear with clues to our environment, the connections of neurons in the amygdala change dynamically in a process called synaptic plasticity.

This physiological mechanism is important for facilitating fear learning, but it has been studied primarily in the context of excitatory neurons in the amygdala. Little is known about the role that inhibitory cells play.

In recent publications Cell report, Bolton Labs MPFI scientists dig deeper into a special part of the amygdala’s inhibitory circuit, the apical insertion cell cluster (apITC). Bolton Labs has discovered this small but distinctive cluster of cells, abundant connectivity and a fairly unique ability to regulate amygdala plasticity.

What caught our attention was the fact that little was known about apITC features and coupling circuits. When working in a relatively unknown brain area, it’s a game of input and output. First, we need to identify what connects to and what connects to the neuron cluster, and then evaluate the functional role that the circuit plays. “

Douglas Asede, Ph.D., Study First Author and Former Postdoc, Bolton Lab

Bolton Lab began its investigation by characterizing and functionally testing incoming connections to apITC.

First, the team used a highly specialized technique called monosynaptic tracing to selectively identify upstream presynaptic partners. Once identified, researchers used a combination of presynaptic optogenetic stimulation (light activation) and postsynaptic electrophysiology to confirm that the connection was functioning.

“We were able to elucidate many diverse inputs to this unique cell cluster, from areas important for memory such as the entorhinal cortex to areas of sensory processing such as the thalamus,” Dr. Asede said. I will explain. “In this diversity, the two notable inputs from the thalamus are their relative strength compared to the other connections we tested, and their origin in the thalamic region, known for their involvement in fear learning. It stood out for. “

The strong connection to apITC comes from two regions of the thalamus, the medial geniculate nucleus (MGm) and the posterior inner core (PIN). Previous studies have shown that MGm and PIN are important processing centers for auditory and somatosensory information, respectively.

In the context of fear learning, input from the thalamus sends sensory information related to fear to the amygdala, which integrates and associates fear with specific clues from the environment.

To investigate whether this flow of sensory information through apITC is important for fear learning, MPFI scientists studied changes in these synaptic connections in mice immediately after behavioral training.

A group of mice underwent classical fear conditioning and behavior-driven changes and were subsequently evaluated using presynaptic and postsynaptic markers of plasticity. Interestingly, the team found significant signs of synaptic enhancement in sensory input to apITC after fear learning when compared to control animals.

“Usually, when synapses are important for a particular behavior, those connections are strengthened during learning, so our results really emphasized the importance of these sensory connections in fear learning,” Asede said. The doctor says.

LA is a region of the amygdala that is strongly associated with fear learning, fear-related sensory integration, and fear-based memory formation. Bolton Lab uses electrical stimulation of thalamic sensory input and optogenetic stimulation of apITC cell input to LA simultaneously to show that activation of apITC acts as a gate to reduce sensory-driven responses in LA. I made it clear.

“With the understanding that apITC is important for sensory gating and fear learning, then what kind of downstream apITC is to give clues about the possible functions of clusters in the amygdala fear circuit. I checked if I could make a connection. “

Classically, inhibitory cells in the brain have been thought to make very short-range downstream connections and act to dynamically alter circuits in their own local environment.

Using axonal reconstruction, Bolton Labs can project most apITC connections to a local axon-side branch to an adjacent apITC or to a nearby area within the amygdala called the lateral amygdala (LA). Has been identified.

Surprisingly, they also identified a subset of relatively long-distance connections to distant brain structures and challenged the classic idea of ​​inhibitory circuits.

“ApITC is one of several clusters of inhibitory neurons that reticulate the amygdala. Each cluster has a unique role in regulating the amygdala’s emotional processing by gating specific inputs. We will do it, “says Dr. Mclean Bolton. Research group leader of MPFI.

“ITC has receptors for many neuromodulators such as dopamine, opiates, and oxytocin, which may act as a barometer for sensing internal conditions and modifying emotions accordingly. This makes ITC a potential target for treatments for anxiety and PTSD. It is important that clusters contribute to opium function. “