New study provides unprecedented insight into the fine details of neuronal communication

There are three main functions of the nervous system: sensory function, which detects changes in the body; integrative function, which makes decisions based on information it receives; and motor function, which carries electrical impulses to stimulate a response. In particular, the integrative functions of the brain bring sensory information together, add to memory, produce thoughts, and make decision.

The cerebellum, part of the brain that is responsible for motor control, serves as an optimal model system to study the integrative features of the nervous system at both the cellular and network level. The circuitry of the cerebellum is strikingly simple when compared with other regions of the brain, with a regularly repeating cellular organization across its outer layer. In addition, cerebellar-dependent tasks have been well-mapped to particular anatomical sub regions. Therefore, the cerebellum offers a unique opportunity to study the dynamics of how information is transferred and transformed within and between neurons to control motor behavior.

Neurons are divided in three main parts: dendrites, axons, and the soma. While dendrites receive and integrate synaptic input, axons transmit the resultant, compiled synaptic information to specific sites in the form of action potentials. Even within these structures there is sub-specialization; dendrites often support functional domains, or dendritic spines, multiplying their computational capacity. And axons achieve a high-degree of specificity in the organization and functional influence of sodium and potassium channels, despite the simplistic classical view of action potentials as monotypic binary pulses transmitted throughout the entire extent of an axon.

In their June 2016 publication in Neuron, researchers Matthew J.M. Rowan, Ph.D., and Jason M. Christie, Ph.D., describe how they overcame a major technical challenge precluding direct examination of axonal excitability. Because of its small diameter -- less than 500 nanometers -- the typical axon can't be examined by the conventional electrophysiological recordings. However, using optically-guided subcellular patching, in combination with organic actuators of neural activity, the scientists were able to sample targeted sub regions of axonal membrane including both presynaptic boutons and their attached axon shafts. This recording configuration allows for the direct assessment of the distribution and biophysical properties of ion channels and receptors expressed along an axon. And, in conjunction, it allows for the direct recording of neural signals including action potentials and subthreshold synaptic activity.

Notably, this study demonstrated that action potentials, often viewed as invariant pulses, are instead quite dynamic with their shape varying with subcellular location. The varicose geometry of boutons, alone, does not impose striking differences in spike duration. Rather, this physiology depends on the differential influence of potassium channel subtypes as well as a clustering of fast-activating potassium channels at presynaptic locations. The organizational feature described by this study allows axons to multiply their adaptive properties by tuning excitation in one axonal domain independent of other domains on an exquisitely local spatial scale, including between neighboring sites of release.

Future directions

According to Dr. Rowan, the clustered arrangement and variable expression density of potassium channels at boutons are key determinants underlying compartmentalized control of action potential width in a near synapse-by-synapse manner. Such organization yields a powerful adaptive property allowing individual release sites to locally inform the duration of a propagating spike, dependent on the local abundance of channels, and separate of other sites. Dr. Christie's research team will further investigate how spike signaling within axons is organized and modified, and the computational value of this organization to cerebellar microcircuits.

Story Source:

The above story is based on materials provided by Max Planck Florida Institute for Neuroscience. Note: Materials may be edited for content and length.

Journal Reference:

Matthew J.M. Rowan, Gina DelCanto, Jianqing J. Yu, Naomi Kamasawa, and Jason M. Christie. Synapse-level determination of action potential duration by K channels in axons.Neuron, June 2016 DOI: 10.1016/j.neuron.2016.05.035

Source : Science Daily

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Natural molecule could improve Parkinson's

These are brain scans of a representative patient showing Dopamine transporter binding (red) before and after 3-month NAC treatment. (Thomas Jefferson University)

The natural molecule, n-acetylcysteine (NAC), with strong antioxidant effects, shows potential benefit as part of the management for patients with Parkinson's disease, according to a study published in the journal PLOS ONE. Combining clinical evaluations of a patient's mental and physical abilities with brain imaging studies that tracked the levels of dopamine, the lack of which is thought to cause Parkinson's, doctors from the Departments of Integrative Medicine, Neurology, and Radiology, at Thomas Jefferson University showed that patients receiving NAC improved on both measures.

Current treatments for Parkinson's disease are generally limited to temporarily replacing dopamine in the brain as well as some medications designed to slow the progression of the disease process. Recently, researchers have shown that oxidative stress in the brain may play a critical role in the Parkinson's disease process, and that this stress also lowers levels of glutathione, a chemical produced by the brain to counteract oxidative stress. Studies in brain cells showed that NAC helps reduce oxidative damage to neurons by helping restore the levels of the antioxidant glutathione. NAC is an oral supplement that can be obtained at most nutrition stores, and interestingly also comes in an intravenous form which is used to protect the liver in acetaminophen overdose.

"This study reveals a potentially new avenue for managing Parkinson's patients and shows that n-acetylcysteine may have a unique physiological effect that alters the disease process and enables dopamine neurons to recover some function," said senior author on the paper Daniel Monti, M.D., M.B.A., Director of the Myrna Brind Center of Integrative Medicine, and the Brind-Marcus Center of Integrative Medicine at Thomas Jefferson University.

In this study, Parkinson's patients who continued their current standard of care treatment, were placed into two groups. The first group received a combination of oral and intravenous (IV) NAC for three months. These patients received 50mg/kg NAC intravenously once per week and 600mg NAC orally 2x per day on the non IV days. The second group, the control patients, received only their standard of care for Parkinson's treatment. Patients were evaluated initially, before starting the NAC and then after three months of receiving the NAC while the control patients were simply evaluated initially and three months later. The evaluation consisted of standard clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS), a survey administered by doctors to help determine the stage of disease, and a brain scan via DaTscan SPECT imaging, which measures the amount of dopamine transporter in the basal ganglia, the area most affected by the Parkinson's disease process. Compared to controls, the patients receiving NAC had improvements of 4-9 percent in dopamine transporter binding and also had improvements in their UPDRS score of about 13 percent.

"We have not previously seen an intervention for Parkinson's disease have this kind of effect on the brain," said first author and neuro-imaging expert Andrew Newberg, M.D., Professor at the Sidney Kimmel Medical College at Jefferson and Director of Research at the Myrna Brind Center of Integrative Medicine. The investigators hope that this research will open up new avenues of treatment for Parkinson's disease patients.

Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.

Journal Reference:

Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Jingli Cai, Xiatao Wei, Anthony J. Bazzan, Li Zhong, Brendan Bowen, Charles M. Intenzo, Lorraine Iacovitti, Andrew B. Newberg. N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data.PLOS ONE, 2016; 11 (6): e0157602 DOI:10.1371/journal.pone.0157602

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