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anatomy of brain

Researchers figure out why we remember some incidents for a long time and forget some

It often happens that we can remember something which occurred long back but forget the incident that took place recently. Some memories remain stable while others fade away in minutes.

Researchers from Caltech have found that the memories which remain stable over time are encoded by a group of neurons firing in synchrony thus providing redundancy. The work also tries to understand the effects on memory after tragic events such as brain damage or Alzheimer’s disease.

The experiments were carried out in the laboratory of Carlos Lois, a biology professor and affiliated faculty member of Tianqiao and Chrissy Chen Institute for Neuroscience. It appears in the Science journal.

The team was led by Walter Gonzalez, a postdoc scholar. A test was developed for testing the neural activity of mice when they learn and remember a new place. The mouse was kept in a straight enclosure of length 5 feet. Different symbols were marked in different locations on the walls such as a bold plus sign at the rightmost end and angled slash close to the center. Sugar water was placed at the track ends. As the mouse explored places, the activities of certain neurons in the hippocampus were tracked by the scientists.

When initially placed in the track, the mouse wandered till it found the sugar water. Single neurons were activated when it spotted a symbol on the wall. However, on staying longer, the mouse remembered the sugar locations. As the familiarity increased more neurons got activated in synchrony as it spotted the symbols.

To understand the fading of memories, the mice were kept away from the track for 20 days. On getting back to the track, the mice which had strong memories encoded by high numbers of neurons remembered the task easily. So when large groups of neurons encode an activity, the memories can be easily recalled even if some showed different activity or remained silent.

This can be explained in a way similar to how a long story is remembered. For remembering a long story, it can be told to many different people and when all of them gather each can fill in the gaps which the other member has forgotten. By repeating this every time, the story can be preserved with the strengthening of the memory. In a similar way, neurons help each other in encoding memories which stay over time.

Impairment of memory in any form can affect us a lot since our life is basically driven by memories. Senior citizens get affected by this as a part of the aging process. Alzheimer’s disease also has devastating effects which paralyze even the basic daily functioning of a person. When memory is encoded by fewer neurons it can be forgotten easily. As a result of this, treatments which increase the recruitment of a large number of neurons for encoding a memory help in preventing memory loss.

When an activity is practiced a lot, there are more chances of remembering it as more neurons are encoded for the action. It is usually considered that to make a memory stable, individual connections to a neuron have to be strengthened. However, the study suggests that the memory can be stored for a long period of time with an increase in the neurons which encode it.

Research Paper: Persistence of neuronal representations through time and damage in the hippocampus

Marathon-running molecule could speed up the race for new neurological treatments

Marathon-running molecule could speed up the race for new neurological treatments

  • Two proteins that activate the fastest molecule in our nerve cells identified by researchers at University of Warwick
  • Mechanism is responsible for transport through our nervous system
  • Faults in cargo transporters can lead to hereditary spastic paraplegia (HSP) and other neurodegenerative disorders
  • Could lead to therapeutic treatment for people with HSP and neurological disorders

Scientists at the University of Warwick have discovered a new process that sets the fastest molecular motor on its marathon-like runs through our neurons.

The findings, now published in Nature Communications, paves the way towards new treatments for certain neurological disorders.

The research focuses on KIF1C: a tiny protein-based molecular motor that moves along microscopic tubular tracks (called microtubules) within neurons. The motor converts chemical energy into mechanical energy used to transport various cargoes along microtubule tracks, which is necessary for maintaining proper neurological function.

Neurons are cells that form the basis of our nervous system, conducting the vital function of transferring signals between the brain, the spinal cord and the rest of the body. They consist of a soma, dendrites, and an axon, a long projection from the cell that transports signals to other neurons.

Molecular motors need to be inactive and park until their cargo is loaded onto them. Neurons are an unusually long (up to 3 feet) type of nerve cell, and because of this marathon distance, these tiny molecular motors need to keep going until their cargo is delivered at the end.

Insufficient cargo transport is a crucial cause for some debilitating neurological disorders. Faulty KIF1C molecular motors cause hereditary spastic paraplegia, which affects an estimated 135,000 people worldwide. Other studies have also found links between defective molecular motors and neurological disorders such as Alzheimer’s disease and dementia.

The research shows how, when not loaded with cargo, KIF1C prevents itself from attaching to microtubule tracks by folding on to itself. The scientists also identified two proteins: PTNPN21 and Hook3, which can attach to the KIF1C molecular motor. These proteins unfold KIF1C, activating it and allowing the motor to attach and run along the microtubule tracks – like firing the starting pistol for the marathon race.

The newly identified activators of KIF1C may stimulate cargo transport within the defective nerve cells of patients with hereditary spastic paraplegia, a possibility the team is currently exploring.

Commenting on the future impact of this research, Dr Anne Straube from Warwick Medical School said: “If we understand how motors are shut off and on, we may be able to design cellular transport machines with altered properties. These could potentially be transferred into patients with defect cellular transport to compensate for the defects. Alternatively they can be used for nanotechnology to build new materials by exploiting their ability to concentrate enzymes or chemical reagents. We are also studying the properties of the motors with patient mutations to understand why they function less well.

“We still know very little about how motors are regulated. There are 45 kinesins expressed in human cells, but we only have an idea how the motors are activated for less than a handful of them. KIF1C is the fastest motor in neurons and the motor that is the most versatile – it delivers cargoes efficiently to all processes in a neuron, not just the axon.”

Journal: https://www.nature.com/articles/s41467-019-10644-9

Materials provided by University of Warwick

Unraveling the brain’s reward circuits

Unraveling the brain’s reward circuits

To some, a chocolate cake may spark a shot of pleasure typically associated with illicit drugs. A new study by Penn biologists offers some insights into that link, revealing new information about how the brain responds to rewards such as food and drugs.

In the work, which appears this week online in the journal Neuron, a team led by Assistant Professor J. Nicholas Betley, postdoctoral researcher Amber L. Alhadeff, and graduate student Nitsan Goldstein of the School of Arts and Sciences shows that, in mice, consuming food turns down the activity of neurons that signal hunger in the brain via a different pathway than alcohol and drugs, which can likewise act as appetite suppressants. Yet the research also reveals that the circuits that trigger the pleasurable release of dopamine are interconnected with the activity of hunger neurons, suggesting that drugs and alcohol can hijack not only the brain’s reward circuits but also those responsible for signaling hunger, serving to create a behavior that reinforces itself.

“Signals of reward, whether it’s food or drugs, access the brain through different pathways,” says Betley, senior author on the work. “But once they’re in the brain, they engage an interconnected network between hypothalamic hunger neurons and reward neurons. It could be that drugs are reinforced not only by increasing a dopamine spike, but also by decreasing the activity of hunger neurons that make you feel bad.”

With a greater understanding of these pathways, the researchers say their findings could inform the creation of more effective weight loss drugs or even addiction therapies.

Betley and colleagues’ work has previously shown infusing any type of macronutrient (any calorie-containing food) into a mouse turned down the activity of AgRP neurons, which are responsible for the unpleasant feelings associated with hunger. The signal by which the stomach tells the brain it has consumed food travels along what is known as the vagal nerve.

Curious about whether alcohol, which is also caloric, could trigger the same effect, they found that it did so in mice, even when the vagal pathway was disrupted.

“If we cut that highway, highly caloric and rewarding foods like fat can no longer get that signal to the hunger neurons, but ethanol could,” says Alhadeff.

The team next tried to do the same thing with cocaine, nicotine, and amphetamine, drugs that have been shown to have appetite suppressing activity, and found the same thing. It’s the first time, the team says, that a non-nutrient has been shown to regulate AgRP neurons for a sustained period of time.

“What is exciting is that the results suggest there are pharmacological mechanisms out there that can be harnessed to reduce the activity of these neurons to alleviate hunger if someone was on a weight-loss diet,” Alhadeff says.

Knowing that alcohol and drugs also trigger the release of dopamine, a neurotransmitter associated with a sensation of “reward” that is also implicated in addiction, the team observed that dopamine neuron activity increased in parallel to the decrease in AgRP neuron activity.

They went after that lead. Using a technique by which they could activate AgRP neurons without depriving an animal of food, the researchers explored how these hunger neurons influence dopamine signaling. In the absence of a food reward, they found little response in the dopamine neurons to activation of AgRP neurons. But when an animal with active AgRP was fed, the surge of dopamine was even higher than it would have been normally, without activated AgRP neurons. In other words, AgRP neurons made food more “rewarding” when the animals were hungry.

“We were surprised to find these AgRP neurons seemed to be signaling the dopamine neurons, but we couldn’t detect that until the animal gets the reward,” Goldstein says. “This suggested that either an indirect or modulatory circuit mediates the interaction between hunger and reward neurons in the brain.”

The same thing happened when the animal received a drug, such as nicotine.

Moving ahead, the research team is investigating the differences between the reward signals that come from alcohol and drugs versus food and unpacking the connection they have revealed between the dopamine neurons and AgRP neurons. Using sophisticated new technology, they’ll also be studying individual neurons to see if the effects they’ve observed are due to the activity of small subpopulations of neurons in the brain.

If they’re successful at identifying a new, druggable pathway that could target these linked circuits, Betley says it would be welcome, as many currently available weight-loss drugs have unpleasant side effects such as nausea.

“It’s hard to have somebody adhere to these drugs when they’re feeling poorly,” he says. “Our findings suggest there are multiple ways into the brain, and maybe by combining these strategies we can overcome these problems.”

Materials provided by the University of Pennsylvania