How the brain recognizes change

April 21, 2020

Have you ever gotten a dramatic haircut? Certainly for some who had their heart broken. That is like a silent shouting to call people to spot change in ourselves and find "the new us". Then how does our brain spot change? Recognizing new objects, new people, new environments, and new rules is critical for survival. Though animal studies found that the hippocampus and NMDA receptors, which mediates and regulates excitatory synaptic transmission, are considered important for novelty recognition, the underlying neural circuit and synaptic mechanisms remain largely unclear.

Led by Professor KIM Eunjoon, a research team of the Center for Synaptic Brain Dysfunctions within the Institute for Basic Science (IBS) in Daejeon, South Korea revealed in an animal study a previously unknown role of a presynaptic adhesion molecule to tell the new change by regulating postsynaptic NMDA-type receptor responses at excitatory synapses. "In order to form a synapse and mediate synaptic transmission, postsynaptic receptors should cluster at sites of new synaptic formation and maturation. Little has been known about what "matures" new synapses and whether synapse maturation affects cognitive brain functions such as novelty recognition". Our data suggest that presynaptic PTPσ promotes postsynaptic NMDA receptor responses, thus allowing to recognize new change" explains Kim.

The brain is composed of a large number of neurons, and these neurons are connected through submicron-size structures known as "synapses". Each individual synapses are composed of two parts; the presynaptic structure that releases neurotransmitter, and the postsynaptic structure that responds to the released neurotransmitter through neurotransmitter receptors. Cell adhesion molecules bridge pre- and postsynaptic specializations. Since there are many different types of synaptic adhesion molecules, it is important for correct pairs of pre- and postsynaptic adhesion molecules to form a complex (bridge) and connect correct partners of neurons. After the initial connections, pre- and postsynaptic adhesion molecules organize the maturation of pre- and postsynaptic structures to mediate synaptic transmission.

One of the key synapse maturation processes is the recruitment of postsynaptic neurotransmitter receptors. However, whether and how presynaptic adhesion molecules trans-synaptically regulate the localization and stabilization of postsynaptic neurotransmitter receptors remained largely unclear. Hypothesizing that there is a key presynaptic adhesion molecule that trans-synaptically regulates postsynaptic receptor responses, the research team knocked out PTPσ, a presynaptic adhesion molecule at excitatory synapses in mice to see whether and how this deletion affects synapse formation and function and mouse behaviors.

As described in Figure 1, (Left) researchers tested social ability and social novelty recognition ability in the three-chamber apparatus. APTP-sigma KO mice, or a WT mouse, was exposed to a social target (S1; stranger mouse) and a non-social target (O; object) for 10 min, where both WT and PTP-sigma KO mice showed normal preference for S1 over O, indicative of normal social interaction. In the next session for the test of social novelty recognition, where O was replaced with S2 (a novel social stranger), whereas the WT mouse showed normal preference for S2 over S1, PTP-sigma KO mice showed impaired social novelty recognition, suggesting that PTPsigma promotes normal social novelty recognition. The heat maps represent mouse movements during social approach and social novelty recognition behaviors indicated: locations with red colors indicate the sites of longer stay of the mouse. The graphs indicate quantitative analyses of social approach (left) and social novelty recognition (right).

(Right) In the second set of experiments (in Figure 1), a PTP-sigma KO, or WT, mice were exposed to a stranger mouse (social target, S1) for four consecutive days, during which the subject mouse spent less and less time exploring the social stranger because of the increasing habituation to the stranger and indicative of normal social recognition and memory. On day 5, when S1 is replaced with a novel stranger mouse (S2), the WT subject showed strongly increased social exploration, as shown by time spent in target exploration or chamber, indicative of normal social novelty recognition and exploration, whereas the PTP-sigma KO mouse showed unchanged exploration of S2 (relative to that for S1 on day 4) (shown by a red circle), indicative of impaired social novelty recognition and exploration. In control experiments, time spent for exploring the empty container was unaffected by experimental conditions.

In sum, they found that PTPσ deletion did not affect excitatory synapse formation but strongly suppressed NMDA receptor responses in the hippocampus, a brain region known to regulate learning and memory. In addition, mice lacking PTPσ showed strongly suppressed novelty recognition in various behavioral tests. For instance, PTPσ-mutant mice failed to recognize new objects, new stranger mice, and new rules. These results suggest that presynaptic PTPσ trans-synaptically regulates postsynaptic NMDA receptor responses and novelty recognition in mice.

"The findings suggest that dephosphorylation of some other presynaptic adhesion molecules and certain trans-synaptic mechanisms may underlie the presynaptic PTPσ-dependent regulation of postsynaptic NMDA receptors. However, the underlying molecular mechanisms still need to identified," notes the first author, KIM Kyungdeok.

These results were corroborated by the essentially similar results reported by the group of Dr. Thomas Sudhof at Stanford University in the same journal eLife almost at the same time.

Institute for Basic Science

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to