Tag Archives: hippocampus

Memory in and out

Do we have a system to form memories and another to recall them or are both processes done by the same system in the brain? This has been a long standing question about the hippocampus. ScienceDaily has a report (here) on a paper answering this question. (Nozomu H. Nakamura, Magdalena M. Sauvage. Encoding and reactivation patterns predictive of successful memory performance are topographically organized along the longitudinal axis of the hippocampus. Hippocampus, 2015; DOI: 10.1002/hipo.22491).

The researchers used tags for molecules known to be involved in memory formation and also tags for the ones used in retrieval, they found that the same cells did both jobs. This is not really surprising because the patterns of cortical activity had been shown to be very similar for a particular memory through its formation, strengthening and recalling. These patterns seemed to come from activity in the hippocampus. A single system for formation and recall also makes it easier to understand the ways that memories are changed when they are recalled and used.

For their studies with rats, researchers adapted a standardised word-based memory test for humans, using however scents instead of words. The researchers hid small treats in sand-filled cups. In addition, each cup also contained a different scent, such as thyme or coriander which could be smelled by the rats when searching for the treats. Each training unit consisted of three phases. During the learning phase, researchers presented several scents to the animals. A pause followed, and subsequently a recognition phase. In the latter, the animals were presented the scents from the learning phase as well as other smells. The animals demonstrated that they recognised a scent from the learning phase by running to the back wall of their cage, where they were rewarded with food for the correct response. If, on the other hand, they recognised that a scent had not been presented during the learning phase, they demonstrated it by digging in the sand with their front paws.

Here is the abstract: “An ongoing debate in human memory research is whether the encoding and the retrieval of memory engage the same part of the hippocampus and the same cells, or whether encoding preferentially involves the anterior part of the hippocampus and retrieval its posterior part. Here, we used a human to rat translational behavioural approach combined to high-resolution molecular imaging to address this issue. We showed that successful memory performance is predicted by encoding and reactivation patterns only in the dorsal part of the rat hippocampus (posterior part in humans), but not in the ventral part (anterior part in humans). Our findings support the view that the encoding and the retrieval processes per-se are not segregated along the longitudinal axis of the hippocampus, but that activity predictive of successful memory is and concerns specifically the dorsal part of the hippocampus. In addition, we found evidence that these processes are likely to be mediated by the activation/reactivation of the same cells at this level. Given the translational character of the task, our results suggest that both the encoding and the retrieval processes take place in the same cells of the posterior part of the human hippocampus.”

Virtual reality is not that real

Virtual reality is used in many situations and is often seen as equivalent to actual experience. For example, it is used in training where actual experience is too expensive or dangerous. In science, it is used in experiments with the assumption that it can be compared to reality. A recent paper (Z. Aghajan, L. Acharya, J. Moore, J. Cushman, C. Vuong, M. Mehta; Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality; Nature Neuroscience 2014) shows that virtual reality and ‘real’ reality are treated differently in the hippocampus where spatial mapping occurs. ScienceDaily reports on this paper (here).

It is assumed that cognitive maps are made by the neurons of the hippocampus, computing the distances to landmarks. Of course, this is not the only way a map could be constructed: sounds and echos could give clues, smells could identify places, and so on. To test whether visual clues alone could give the information to create a map, the researchers compared the activity of neurons in the hippocampus in a virtual walk and a real walk that were visually identical. In the real set-up the rat walked across a scene while in the virtual set-up the rat walked on the treadmill while the equivalent visual ‘movie’ was projected all around the rat.

The results showed that the mapping of the two environments was different. The mapping during real experience involved more activity by more neurons and was not random. In the virtual experiment, the activity was random and more sparse. It appeared, using neuron activity, as if the rat could not map virtual reality and was somewhat lost or confused, even though they appeared to be acting normally. “Careful mathematical analysis showed that neurons in the virtual world were calculating the amount of distance the rat had walked, regardless of where he was in the virtual space.

In the same report, other research by the same group is reported. Mehta describes the complex rhythms involved in learning and memory in the hippocampus, “The complex pattern they make defies human imagination. The neurons in this memory-making region talk to each other using two entirely different languages at the same time. One of those languages is based on rhythm; the other is based on intensity.” The two languages are used simultaneously by hippocampal neurons. “Mehta’s group reports that in the virtual world, the language based on rhythm has a similar structure to that in the real world, even though it says something entirely different in the two worlds. The language based on intensity, however, is entirely disrupted.

As a rat hippocampus is very similar to a human one and the virtual reality set up was a very realistic one, this study throws doubt on experiments and techniques that use virtual reality with humans. It is also very interesting to notice another surprising ability of neurons, to process two types of signal at the same time.

Abstract: “During real-world (RW) exploration, rodent hippocampal activity shows robust spatial selectivity, which is hypothesized to be governed largely by distal visual cues, although other sensory-motor cues also contribute. Indeed, hippocampal spatial selectivity is weak in primate and human studies that use only visual cues. To determine the contribution of distal visual cues only, we measured hippocampal activity from body-fixed rodents exploring a two-dimensional virtual reality (VR). Compared to that in RW, spatial selectivity was markedly reduced during random foraging and goal-directed tasks in VR. Instead we found small but significant selectivity to distance traveled. Despite impaired spatial selectivity in VR, most spikes occurred within ~2-s-long hippocampal motifs in both RW and VR that had similar structure, including phase precession within motif fields. Selectivity to space and distance traveled were greatly enhanced in VR tasks with stereotypical trajectories. Thus, distal visual cues alone are insufficient to generate a robust hippocampal rate code for space but are sufficient for a temporal code.

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.