Researchers Pinpoint the cells that control the brain's memory flow

on 07 February 2019
to change life you need the answer to the question

Life makes memories and memories make a life but did you know that some memories can actually break or distort a life? Luckily, there is an effective way to change the way memories express themselves and in the process, life changes. . . . 

Memory, where would we be without it?

The most amazing thing for me, relating to the brain, is that the more you discover, the more you understand how much more there is to discover. Years ago I thought of the hippocampus as one individual part of the brain, only to find out that it is merely the collective name of the whole group of related parts, one of which, is the hippocampus proper, as well as the dentate gyrus, rhinal cortex (inc. perirhinal, entorhinal, parahippocampal gyrus) and the subiculum, which itself has 4 divisions, Pre/post/pro/para-subiculum. This network of regions is primarily seen as the hub of memory processing, i.e. the creation, storage and retrieval of memories, as well as the necessary maps we need to put things in place and context. The hippocampal complex (my own label), is, in fact just one part of an enormous number of brain regions involved in the overall process of memory. And memories are effectively the essence of life itself. Every time a new memory is created the brain gets larger, not so much in terms of volume but, rather, in terms of connections. Almost every new memory is a consequence of adding to an existing circuit or the beginning of new ones. The hippocampus and many of its neighbours play a significant role in these processes.

Relative to this research, the hippocampus proper is made up of the dentate gyrus and 4 areas, i.e. CA1 to CA4 (CA refers to cornu ammonis an older name for the hippocampus). CA1 has output pathways to the entorhinal cortex (EC) and the subiculum (SM). As stated above, the entorhinal cortex, perirhinal cortex, and parahippocampal gyrus make up the rhinal cortex, which in some sense form part of a memory super processing area. The EC is the main interface between the hippocampus and the neocortex. Information from our sensory regions (mostly from the thalamus) flows to the perirhinal and parahippocampal cortices, and then continue into the entorhinal cortex and from there proceed to the dentate gyrus and the hippocampus. The EC has a number of functions, e.g. place fields, made up of grid cells that plot our position in the environment, as well as directional activity (clockwise/counter-clockwise). Essentially this is part of a system that makes the maps and allows you to find your way, e.g. home. work, favourite restaurant etc. The amazing thing about these grid cells is, they actually expand and contract, relative to your environment and consequently, directly or otherwise, are connected to our visual perceptive field. A somewhat useful distinction scientists have made, regarding the entorhinal cortex is, that the medial entorhinal cortex (innermost part), mainly supports the processing of space and the lateral entorhinal cortex (outermost part) mostly supports the processing of time. To test this, close your eyes and touch, the tip of your nose, upper eyelid, under the chin, tip of your shoulder etc, and see how accurately you can locate these parts, this is proprioception (albeit some other brain regions also play a supporting role too)!

The subiculum is equally fascinating and each of its 4 divisions plays a unique role, e.g.

The parasubiculum also has grid cells and works in a distance related way relative to movement and direction. 

The presubiculum has input pathways to the entorhinal and the hippocampal spatial memory system.

The postsubiculum is the dorsal (upper) part of the presubiculum and is important because it contains head direction cells. These cells are responsive to the direction our head is facing. Temporary disruption to this area, e.g. through spinning around, is what results in giddiness.

The presubiculum is mostly noted for its high density of smaller neurons and its position lays between the subiculum proper and the CA1 area of the hippocampus, thus potentially playing some form of relay function. 

The subiculum itself, as a whole, receives input from CA1 and entorhinal cortical layer III pyramidal neurons and is the main output of the hippocampus. The pyramidal neurons send projections to the nucleus accumbensseptal nucleiprefrontal cortexlateral hypothalamusnucleus reuniensmammillary nucleientorhinal cortex and amygdala (source Wikipedia). It is believed (believed because opinions change relative to new research) that the dorsal (upper) part of the subiculum is involved in spatial awareness and the ventral (lower) subiculum regulates the hypothalamic-pituitary-adrenal axis, which precipitates the stress response - fight or flight. Also involved in this process, is the amygdala - for certainty related fear responses - the BNST (bed nucleus of the stria terminalis), for uncertainty related fear responses and is more implicated in its role in anxiety type disorders, as in, the anticipation of danger, not the actual presence of it, as well as the hypothalamus, nucleus accumbens, periaqueductal grey and many higher cortical and subcortical regions of the brain. 

My theory of many of life's challenges is, that they are perceptual but based on an obscure belief that the nebulous "we" represent something separate from and superior to our brain or mind. To clarify that, many of my clients are surprised to discover the way their brain reacts and responds to various stimuli. Some are simple to understand, for example, you wouldn't dream of putting your hand into a pot of boiling water. However, some harmless stimuli can take on all the properties of a harmful one and these become memory-based behavioural responses. This is what happens when scientists pair a bell (the conditioned stimulus) with a foot shock (the unconditioned stimulus) in lab rat experiments. Following repeated and simultaneous exposure to the bell and the shock, once conditioning has taken place, they use only the bell and the lab rat responds to the bell with all the intensity of the shock. If we are in one emotional state of shock or anxiety etc. when we experience something that naturally and instinctively elicits a fear response, the two experiences can be locked into one collective memory that elicits the response when in either position or experience. I have experienced this in many clients who had a fear of flying, especially ones who have flown for many years without incident. And yet, a solution/cure was achieved without even mentioning flying!

My aim here is to highlight the complexity of a function of daily life, called memory, that we take so much for granted and this all happens simultaneously in seconds to milliseconds without us having the slightest awareness of its happenings! Of course, if we were aware we would be overwhelmed emotionally and mentally paralysed and subsequently become inactive. As so much of life is lived in or through our memories, the solution to life's challenges can, naturally, be found in the realm of memories, i.e. in the sleepy dreamlike state, we call hypnosis. So, if you have an issue that is causing you to wish life could be different, why not make an appointment for a Free Consultation and turn your life around - see the link below for more details.

The interesting thing about this research is the observations of VIP cells in the hippocampus. Previously most research on VIP cells was based on their role in the suprachiasmatic nucleus, a part of the hypothalamus. and was most specifically relating to their role in circadian rhythms (the body's 24hr clock) and this fits so nicely into the role of the entorhinal cortex space-time continuum, e.g. time and space etc.

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 sleep and too little by way of 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 mind'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 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! 

The objective here is to help people understand how and why we become illogically trapped into irrational emotional experiences that may actually be happening for reasons different to that which we would imagine! If you want to know more about how Hypnotherapy can help you; 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

From the cab driver heading for Times Square to the commuter returning home on the freeway, we all carry maps in our head labelled with important locations. And a new Columbia study in mice shows that, by directing the delicate ebb-and-flow of brain activity, a small cluster of cells helps the brain's internal GPS remember which places matter most. These findings underscore the fact that navigating an environment requires flexibility in the brain: the brain-cell activity must change as memories are formed or recalled.

This research, published today in Neuron, could also provide insight into psychiatric disorders, such as autism and schizophrenia, which are often characterized by disruptions to this flexibility.

"Memories are fluid, not fixed, but observing precisely how brain cells, or neurons, flexibly lay down or recall memories has long proven challenging to scientists," said Attila Losonczy, MD, PhD, a principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper's senior author. "With today's study, we provide, for the first time, visual evidence that a particular type of neurons makes this flexibility possible."

The brain's headquarters for learning and memory is the hippocampus, and it can be divided into distinct areas that process memory-related information. For this study, the researchers focused on area CA1, which encodes an animal's location -- as discovered by researchers who won the 2014 Nobel Prize.

In 2016, Dr Losonczy's lab found that CA1 neurons can act as a homing beacon; when a mouse looked for something, like water, neural activity spiked as the animal got close.

"The question then became: Was something directing this spike in activity?" said Dr Losonczy, who is also a professor of neuroscience at Columbia's Vagelos College of Physicians and Surgeons.

Broadly speaking, scientists divide neurons into two types: excitatory and inhibitory. Excitatory neurons are the gas pedal; they drive the activity of other neurons. Inhibitory neurons, by contrast, are the brakes: they suppress neural activity.

Today's study focused on a particular type of CA1 inhibitory neurons called vasoactive intestinal polypeptide-expressing, or VIP, cells. Researchers had previously confirmed the existence of VIP cells but had not examined them in the hippocampus of animals as they learned.

Using a two-photon microscope, Dr Losonczy and his team monitored the VIP-cell activity as the mice ran on treadmills laden with various sights and sounds, some familiar and others new. This allowed the researchers to examine how the animals' brains responded as they explored their surroundings, without a particular goal in mind.

In the second set of experiments, the mice were given a task: find a water reward that had been placed at a specific, unmarked location along the treadmill's path.

VIP-cell activity tended to spike during both sets of experiments: first, as the animal ran aimlessly and then during goal-oriented learning when it sought the reward. Additional experiments and computational modelling, undertaken in collaboration with co-senior author Panayiota Poirazi, PhD, revealed how VIP cells heavily influenced CA1 neural activity.

"By default, CA1 excitatory neurons are kept 'off,' by a cluster of neighbouring inhibitory neurons that target and suppress their activity," said Dr Losonczy. "But as the animals learned, the second cluster of inhibitory neurons -- the so-called VIP cells -- sprung to life."

In a sequence of Rube Goldberg machine-like steps, the VIP cells first targeted the cluster of inhibitory neurons, effectively silencing them.

"With the inhibitory neurons no longer suppressing their activity, the excitatory neurons were then free to switch on," said Dr Losonczy. "This set off a chain reaction; activating the entire CA1 memory circuit and, ultimately, allowing the animals to learn.

As a reflection of this stepwise mechanism, Dr Losonczy classifies VIP cells as disinhibitory neurons, because they act by inhibiting the inhibitory neurons. Disinhibition thus appears to be an ingenious way in which excitatory neurons can -- in a roundabout way -- be activated.

Though disinhibition may seem counterintuitive, Dr Losonczy argues that it is actually illustrative of the delicate and fine-tuned nature of learning. A simple circuit -- with one on-off switch -- would be too blunt. An added layer of complexity may have evolved to match the complex nature of memory. This complexity also gives the circuit added flexibility when choosing which groups of neurons get activated, thus providing an additional, subtle way of adjusting itself during learning.

Moving forward, the research team will continue investigating VIP cells, as well as other cell types in the hippocampus involved in learning. They are also optimistic about what these findings mean for understanding disorders in which disrupted neural circuitry has been implicated.

"Normal brain function requires a delicate balance of excitation and inhibition, but many neuropsychiatric disorders, such as schizophrenia and autism, are characterized by an imbalance in this type of neural activity," said Dr Losonczy. "Our work and the work of others could very well help to elucidate how these disruptions result in these disorders' devastating symptoms."

Additional contributors include co-first authors Gergely Farkas Turi, PhD, and Wen-Ke Li, PhD, Spyridon Chavlis, Ioanna Pandi, Justin O'Hare, PhD, James Benjamin Priestley, Andres Daniel Grosmark, PhD, Zhenrui Liao, Max Ladow, Jeffrey Fang Zhang and Boris Valery Zemelman.

This research was supported by the National Institute of Mental Health (1R01MH100631, 1U19NS104590, 1R01NS094668, F32MH18716, U01NS094330, U01NS099720), the Zegar Family Foundation, New York State Stem Cell Science (NYSTEM-C029157, S10OD0184464), the Revson Foundation and the ERC Starting Grant Demory (ERC-2012-StG-311435).

Story Source:

Materials provided by The Zuckerman Institute at Columbia UniversityNote: Content may be edited for style and length.

Journal Reference:

  1. Attila Losonczy et al. Vasoactive intestinal polypeptide-expressing interneurons in the hippocampus support goal-oriented spatial learningNeuron, 2019 DOI: 10.1016/j.neuron.2019.01.009

Cite This Page: The Zuckerman Institute at Columbia University. "Pinpointing the cells that control the brain's memory flow." ScienceDaily. ScienceDaily, 31 January 2019. <>.