Tag Archives: neurons

More about neurons

I want to make a point here that we know less about the brain than is generally acknowledged. Our picture of the functioning of a neuron is taken as more or less settled knowledge; only small refinements are likely. But the refinements that are regularly published are not small. Now we have a paper (citation below) that is extraordinary.

Bywalez and others have shown that the little spines on the dendrite trees of neurons can themselves act as miniature neurons accomplishing computations similar to a full neuron (at least in the olfactory bulb part of the brain and probably other parts too) and that some synapses can be two sided, transmitting signals in both directions. This allows dendrite to dendrite communication. In effect the neck of the spine can isolate the spine from the rest of the neuron, allowing it to reach an action potential level of voltage in its area without interference from the rest of the dendrite tree, and so it is able to send a signal backwards out of the spine.

classic neuron

classic neuron

We are used to thinking of neurons as, in effect, huge add-gates that take a multitude of synapses giving inputs of various strengths and those inputs are combined in the dendrites into a voltage level in the main cell body. If that voltage is above a threshold, an action potential voltage, a signal, is propagated down the neuron’s axon to the dendrites other, usually distant, neurons. There it influences how those other neurons act by contributing a positive or negative voltage to the receiving dendrites’ totals. It is fairly easy to imagine how this works and to mimic it with electronic circuits.

But neuroscience keeps finding exceptions to this theory. There are glial cells assisting and interfering with the process and they can communicate with each other by a different mechanism. There are signals that bypass the whole dendrite calculation and input their signal at the cell body root of the axon, thereby over-riding other inputs. There are axon to axon synapses. Neurons can multitask by calculating and then sending two separate message codes to two separate groups of receiving neurons. Signals can go backwards up the axon. Some neurons can learn timing delays in their signaling. And now this: action potentials can be generated in the little spines of the dendrites and some synapses are not one way transmitters with pre and post halves, but can work both ways. The standard model is getting tattered with exceptions. No doubt there are many more exceptions to come. I venture that we are nowhere near understanding neurons and neuron network behavior.

Bywalez, W., Patirniche, D., Rupprecht, V., Stemmler, M., Herz, A., Pálfi, D., Rózsa, B., & Egger, V. (2015). Local Postsynaptic Voltage-Gated Sodium Channel Activation in Dendritic Spines of Olfactory Bulb Granule Cells Neuron DOI: 10.1016/j.neuron.2014.12.051

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Another new neuron type


In a press release (here) about a Neuron Journal paper (see citation below), it was announced that there were neurons in the hippocampus with a newly discovered anatomy, in fact they are common there.

The model of a neuron is that it has a cell body with branches (dendrites) in one area that receive input from other neurons and a long extension (axon) that has branches at its end to output signals to other neurons. The standard picture is that there is a complex summation of synaptic inputs on the dendrite branches and then a summation on the body of the cell of the dendrites which either reaches the threshold for firing or not. If threshold is reached the activity travels down the axon to the synapses with other neurons.

The newly discovered neurons have a bypass, shunt or privileged path. The axon in these cells does not start on the cell body but on a dendrite that is on the axon side of the cell body. Therefore input to this particular dendrite does not have to pass though the cell body but can directly send signals down the axon. This axon can fire if the dendrite it is attached to reaches threshold or if the cell body reaches threshold due to activity on the other dendrites.

A metaphor might be like this. The decision whether or not to fire is taken by small committees with pro and con members, then the results of those committees goes to a higher committee. If that committee decides to fire then firing will happen. On the other hand, the boss and his advisors can just walk in and order fire if they choose.

These pyramid cells in the hippocampus would have an important role in memory. What the function of this arrangement is has not yet been researched.

Here is the abstract:

Neuronal processing is classically conceptualized as dendritic input, somatic integration, and axonal output. The axon initial segment, the proposed site of action potential generation, usually emanates directly from the soma. However, we found that axons of hippocampal pyramidal cells frequently derive from a basal dendrite rather than from the soma. This morphology is particularly enriched in central CA1, the principal hippocampal output area. Multiphoton glutamate uncaging revealed that input onto the axon-carrying dendrites (AcDs) was more efficient in eliciting action potential output than input onto regular basal dendrites. First, synaptic input onto AcDs generates action potentials with lower activation thresholds compared with regular dendrites. Second, AcDs are intrinsically more excitable, generating dendritic spikes with higher probability and greater strength. Thus, axon-carrying dendrites constitute a privileged channel for excitatory synaptic input in a subset of cortical pyramidal cells.

Citation: C. Thome, T. Kelly, A. Yanez, C. Schultz, M. Engelhardt, S. B. Camebridge, M. Both, A. Draguhn, H. Beck and A. V. Egorov (2014): Axon-Carrying Dendrites Convey Privileged Synaptic Input in Hippocampal Neurons. Neuron, 83, 1418-1430.

A new feature of neurons

There are articles asking, “Are we ever going to understand the brain?” They imply that we have been studying the brain for long enough to be able to say how it works, if we are ever going to, and therefore hinting that it is a permanent mystery. But every week or so some new wrinkle on the brain’s nature comes to light. The brain is far more complicated and far less understood than many think.

Recently a paper appeared that pointed to a wholly new feature of neurons. (citation below) Johansson and his colleagues demonstrate a surprising feature of at least some neurons. They looked at a well known response. When a puff of air is directed at the eye, there is a blink. If this is done over and over with the same time interval between a signal and the puff, a reflex is formed so that the blink happens at just the right time to protect the eye from the puff. This is a standard conditioned reflex and we thought we understood conditioned reflexes. The researchers found that the learning of the time between signal and puff was not a function of a network of cells but an internal function of one type of cell. “The data strongly suggest that the main timing mechanism is within the Purkinje cell and that its nature is cellular rather than a network property. Parallel fiber input lacking any temporal pattern can elicit Purkinje cell responses timed to intervals at least as long as 300 ms. … In addition, the data show that a main part of the timing of the conditioned response relies on intrinsic cellular mechanisms rather than on a temporal pattern in the input signal. ” We have been modeling neurons as firing, or not, as a result of the strength of the signals at their synapses; and firing, if they do, immediately. Any timing effects were assumed to be produced by network structures. Neurons were modeled as very fancy switches but with no timing capabilities. Now understanding has changed. Large changes in understanding, like this one, happen regularly. We are a long way from understanding the mechanisms in the brain.

Here is the Significance and Abstract:

The standard view of neural signaling is that a neuron can influence its target cell by exciting or inhibiting it. An important aspect of the standard view is that learning consists of changing the efficacy of synapses, either strengthening (long-term potentiation) or weakening (long-term depression) them. In studying how cerebellar Purkinje cells change their responsiveness to a stimulus during learning of conditioned responses, we have found that these cells can learn the temporal relationship between two paired stimuli. The cells learn to respond at a particular time that reflects the time between the stimuli. This finding radically changes current views of both neural signaling and learning.

The standard view of the mechanisms underlying learning is that they involve strengthening or weakening synaptic connections. Learned response timing is thought to combine such plasticity with temporally patterned inputs to the neuron. We show here that a cerebellar Purkinje cell in a ferret can learn to respond to a specific input with a temporal pattern of activity consisting of temporally specific increases and decreases in firing over hundreds of milliseconds without a temporally patterned input. Training Purkinje cells with direct stimulation of immediate afferents, the parallel fibers, and pharmacological blocking of interneurons shows that the timing mechanism is intrinsic to the cell itself. Purkinje cells can learn to respond not only with increased or decreased firing but also with an adaptively timed activity pattern.

Johansson, F., Jirenhed, D., Rasmussen, A., Zucca, R., & Hesslow, G. (2014). Memory trace and timing mechanism localized to cerebellar Purkinje cells Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1415371111

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