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Researchers now have an idea of how the brain recognises change
on 26 April 2020
The Memory Puzzle

Life doesn't just happen, it's an intricate lifelong journey of learning and adapting to a myriad of experiences, from birth to the day you decide to do something about it! Something that puts 'You' in control of that journey, is Hypnotherapy. That's simply because it is one of the most effective methods of discovering exactly how much you can control the way your life unfolds . . . 

My interest in this research is linked to my hypnotic speciality, i.e. stress (anxiety). The research shows the role played by presynaptic PTPσ (protein-tyrosine-phosphatase_sigma), in the way it has a regulating effect on excitatory NMDARs (N-methyl-D-aspartate receptors). NMDARs are glutamate (excitatory) receptors and the most abundant in the human brain. They are also Ion_Channel proteins, which play a role in various cell functions, e.g. resting/action potential and electrical signal gating functions. Glutamate can be usefully seen as the on-switch, whereas its inhibitory counterpart, GABA (gamma-aminobutyric acid), is the off-switch. NMDARs are adversely affected by glucocorticoids (stress hormones), especially in the hippocampus.

The hippocampus plays a significant role in memory and is rich in glucocorticoid receptors, meaning, it is very adversely affected by a highly, ongoing (chronic) stressful situations. The dentate gyrus, a part of the hippocampal region, is also the birthplace of neural stem cells (NSC) and the quantity and quality of these NSCs are paramount to the way our brain functions, specifically relating to memory and learning. The effects of this can be observed in children and parents during PLSE time. Stress affects our ability to form new memories and/or recall existing ones, this is known as test/exam anxiety. It also affects the quantity of NSC production and the process of turning the stem cells into new neurons, essential for learning new things and updating current knowledge.

The essence of this research emphasises the need to reduce unnecessary stressors in our life, the emphasis being, "the unnecessary stressors!" Ordinary stress is both normal and essential to life. It plays a very significant role in our immune system and our protective defensive behaviours. It could, probably has, saved your life on many occasions but . . . like anything else, it is capable of being disrupted, and if this happens too often, for too long, it can become disordered. Anxiety, as a disorder, is a condition that involves the presence of stress hormones and the stress response (fight or flight). In a general sense, stress occurs when we are faced with a real or perceived danger, and it triggers a response that puts our systems on high alert; we are primed and ready for action. Anxiety, on the other hand, initiates the stress response, in anticipation of a dangerous or threatening situation. For example, you are on an aeroplane, and it suddenly drops (clear air turbulence), your heart starts to pound, a sense of dread overwhelms you, that's fear (stress). Alternatively, you just finished booking your flight, your heart starts to pound, that same overwhelming feeling pervades, that's anxiety and you are also in the stress response). The flight experience elicits a survival response, however, it is aggravated because, at 39,000 feet, you can neither fight or run. A consequence of this is that your brain stores an emotional memory of the event. When it comes to booking your next flight, pressing that "Book Now" button elicits the memory of that, flight, experience. Of course, this doesn't happen like this to 'all people' on 'all flights,' it just happens to some of us! However, those of us that develop this kind of fear response, will very often have had some history of anxiety, maybe even some form of depressive disorder too?

Hypnotherapy has an excellent history at being able to help clients resolve unnecessary levels of stress hormones, thus returning the production of NSC to their normal levels. However, it also has the ability to create greater states of calmness and it is in the calmness that we discover the inner peace that allows the presynaptic PTPσ (protein-tyrosine-phosphatase_sigma), to do its magic! When this happens, NMDARs and their cousins (AMPA/Kainate receptors) also do their job and we begin to function the way we are designed to. Life, therefore, is not in how we manage stress but rather, in how well we manage states of calmness! So, if you want to perform, reach your zenith, be in the zone, the flow or any other well-known euphoric state of being, why not book an appointment for a Free Consultation?

Hypnotherapy stands out as one of the most effective strategic life management methods there is, especially in its ability to promote clear thinking and good states of mental wellness. The behaviours that make life challenging are often a result of too much stress, too little or poor quality sleep and too little by way of mental and emotional clarity! So, to get or take back control of your mind and your life, it makes perfect sense to use a methodology that addresses the subconscious brain's role in perpetuating negative, vague and ambiguous states of mind. Hypnosis helps us to create calm relaxing states of mind that make life work better! If you would like to address any concerns you have in this direction, or, if you just want the ability to make your life feel better, then why not make an appointment for a Free Consultation? Hypnosis gives you the ability to have a good life! 

My objective is to help people understand how and why we become illogically trapped into emotional experiences that may actually be happening but for reasons, we may never have imagined! If you want to know more about Hypnotherapy, why not make an appointment for a Free Consultation?

For more information on the Free Consultation - Go Here Or, to book your Free Consultation today, you can do so here


The Research:

Synaptic adhesion molecule regulates postsynaptic responses and novelty recognition in mice!

Have you ever gotten a dramatic haircut? Certainly for some who had their heartbroken. That is like a silent shouting to call people to spot the 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 are 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 a 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 behaviours.

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 a 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 a 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 behaviours indicated: locations with red colours 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, 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, the time spent on 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 behavioural 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 identify," 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.


Story Source:

Materials provided by the Institute for Basic ScienceNote: Content may be edited for style and length.

Journal Reference:

  1. Kyungdeok Kim, Wangyong Shin, Muwon Kang, Suho Lee, Doyoun Kim, Ryeonghwa Kang, Yewon Jung, Yisul Cho, Esther Yang, Hyun Kim, Yong Chul Bae, Eunjoon Kim. Presynaptic PTPσ regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanismseLife, 2020; 9 DOI: 10.7554/eLife.54224

Cite This Page:

Institute for Basic Science. "How the brain recognizes change: Synaptic adhesion molecule regulates postsynaptic responses and novelty recognition in mice." ScienceDaily. ScienceDaily, 21 April 2020. <www.sciencedaily.com/releases/2020/04/200421112533.htm>.