Neurons in mouse piriform cortex contribute to development of recurrent circuits, study finds

The activity of neurons in the mammalian brain is known to contribute to brain development from early stages of development. Although previous neuroscientific studies have gathered evidence supporting this notion, the extent to which early neuronal activity regulates the maturation of neural circuits has not yet been fully determined.

Researchers from Stanford University and Duke University School of Medicine conducted a study exploring how neurons in the mouse brain contribute to the formation of connections between cortical regions during development. Their findings, published in Neuronhighlight the key role of neurons in the mouse piriform cortex, a brain region that supports the processing and encoding of olfactory information, in the development of recurrent neural circuits.

“We were interested in the general question of how neuronal activity shapes brain wiring during development,” Liqun Luo, supervising author of the paper, told Medical Xpress. “This question has previously been studied in the context of how peripheral sensory information, such as vision and touch, shapes the brain circuits that process these peripheral inputs. However, little was known about how the Activity within the brain itself shapes neurological development early in life.

Determining which neurons are most active in a developing mammalian brain, particularly before an animal is born, has so far proven very difficult. Luo and colleagues recently developed a new technique that can be used to reliably assess neuronal activity levels in the prenatal and early mouse brain, which they called targeted recombination in active populations (TRAP) .

“Using this new technique, we first studied which neurons are particularly active in the embryonic brain, before the mice receive external sensory information,” Luo said. “We discovered that the embryonic olfactory cortex is particularly active and decided to determine what functions these active neurons might serve in the brain’s wiring.”

We first asked whether our active embryonic neurons have distinct connectivity within the brain, as this can often provide clues about their function. To do this, we tested whether embryonicly active neurons are preferentially connected to each other compared to nearby control neurons, and found that they are.

“These early experiments were performed in vitro on brain slices, which allowed us to easily perform electrophysiological recordings,” explained Kevin M. Franks, co-senior author of the paper.

“We then tested in vivo in young mice what types of odors these embryonicly active olfactory cortex neurons are sensitive to. We suspected that they might be particularly sensitive to odors from the neonatal environment, such as odors of mother and milk which are important for the newborn mouse.

Initially, the team hypothesized that active pyriform cortex neurons in mouse embryos would be more responsive to odors present in the newborn’s environment, such as that of breast milk. Yet their findings refuted this hypothesis, as these neurons in the olfactory cortex were found to be attuned to a wide range of sensory stimuli.

“This combination of broad connectivity and broad sensory tuning led us to hypothesize that the function of these embryonically born neurons is perhaps that of a network hub, important in facilitating maturation of connectivity between the olfactory cortical neurons themselves, what’s called recurrent connectivity, which is very strong in the adult olfactory cortex,” Franks said.

“In short, our experiments (including analysis of in vivo firing patterns, both in response and in the absence of odor, as well as the consequences of artificial activation and inhibition) have strongly supported this hypothesis.

The results collected by the researchers suggest that early activity of neurons in the mouse piriform cortex plays a key role in the maturation of intracortical connectivity, a novel finding given that most previous studies have focused on the maturation of circuits involved in the initial processing of sensory information. information.

Instead of simply refining sensory inputs, neuron activity could thus shape the architecture of the cortex itself, which in turn would influence how the brain represents sensory inputs.

“Our study expands the role of neuronal activity in brain wiring,” said David C. Wang, first author of the paper.

“It also provides in vivo evidence for ‘core neurons’ – particularly active neurons with broad connectivity that had previously only been reported ex vivo – and their function in circuit maturation. This recurrent connectivity that our central neurons influence is involved in various phenomena includes the processing of sensory information (i.e. associating similar sensory inputs or distinguishing different ones) as well as uncontrolled arousal during seizures.

Recent work by Luo, Franks, Wang and colleagues provides evidence that a relatively small group of neurons could influence early brain development. Notably, the team’s findings were collected using cutting-edge experimental methods, including TRAP, recording of in vivo neuronal activity, and non-invasive optogenetic techniques.

The recent study is the result of a collaborative effort combining expertise from separate research laboratories at Stanford and Duke. Wang, MD/Ph.D. A student who was then part of Luo’s lab performed the in vivo experiments in Franks’ lab at Duke University over an 8-month period.

“Our study highlights the power of scientific collaboration,” Wang said. “Without the combination of the expertise of the Luo and Franks labs and many stimulating conversations between the two labs, this would not have been possible.”

The recent work by Wang, Franks, Luo and their collaborators may soon pave the way for new experiments aimed at examining in more detail the contribution of neurons in the mouse piriform cortex to the maturation of brain circuits. Meanwhile, researchers are conducting other studies exploring the function of active embryonic neurons in other regions of the brain.

“We are now also investigating the effects of postnatal experience on the wiring and function of the olfactory cortex, particularly in the context of learning and memory for odors,” Franks added.

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