Filed under: science | Tags: entorhinal cortex, fyhn, grid cells, moser, theta, transgenics
In preparation for transgenic studies of the entorhinal cortex, the Moser lab (out of Trondheim, Norway) released a paper this month outlining the similarities between grid cells in mice and the better characterized grid cells in rats. Grid cells were discovered fairly recently. They fire when a rat is in specific spatial locations, but unlike place cells, there are many firing locations for one grid cell and the locations form a hexagonal grid. This system may provide a coordinate system for navigation and may inform the more specific spatial coding system in the hippocampus. The entorhinal cortex is, of course, directly upstream of the hippocampus in the hierarchical funnel of information processing that makes up the medial temporal lobe (if you believe in that sort of thing.. hierarchies… i mean.. in the brain..).
Items of note.
Theta power jumps abruptly as electrodes move from the postrhinal to the entorhinal cortex. Theta is either generated by intrinsic rhythmic properties of local interneurons or principal cells OR by rhythmic input from extrinsic afferents from the hippocampus or perhaps the medial septum (he said, not knowing for sure if the septum projects there). My gut goes toward the latter because it isn’t easy to imagine a large change in membrane properties of cell populations that develop right next to each other. OTOH, one little ion channel or neuromodulator receptor (or calcium-buffering protein?) could do the trick. In any case, it will be interesting to see this replicated and determine if any innervation patterns or physiological variables correlate with the topographical theta power function.
Not a finding from this study, but cited. van Groen et al. showed that the wiring diagram for the C57BL/6J strain of mice is unusual. This will be a hindrance in interpreting studies that use only this strain, but will be of interest as a possible “natural experiment” to understand the evolution and function of the particular altered projection.
Grid sizes are similar between mouse and rat. This means that the grid coding isn’t about self-motion cues or how long a rat’s leg is. I have to think about what this means more. It’s not immediately apparent why one grid size would suit a rodent better than another. It’d sure be interesting to know what human grid sizes are.. or at least monkeys. Maybe we could use a virtual environment.
The lab is clearly on the verge of some very interesting transgenic studies. Reading their discussion, it is apparent that they are excited about reversible activation or inactivation of specific neuronal populations. Every new study on the genetics of cortical development brings us closer to having control over every distinct cell-type individually. Adding in viral gene delivery allows spatial control in the absence of specific developmental knowledge. Technologies are already available for inactivation using inducible genetic systems tied to proteins involved in synaptic physiology (for instance, Tonegawa’s tetanus-toxin mouse). These are great, but the timing is still not precise. Waiting for the genetic induction can take weeks. Another generation is on the verge, using light controlled ion channels. The major technical hurdle in my mind was how to get the right kind of light inside the right part of the skull, and I think that may have just been taken care of. The Moser Lab will be interested in controlling activity in the entorhinal cortex with these techniques, but I hope they will also avail themselves of other important transgenic methods such as monosynaptic retrograde tracing and activity-dependent cell tagging. Looking forward to hearing about the studies that this report suggests are underway.
Siik.org is where I get dope remixes that my friends don’t know about. He updates in spurts, so I consume in spurts. Just noticed his mix of Brandy - I wanna be down. I’m not sure if it’s bad etiquette for me to throw it in the flash player. I’ll email him and ask.
Also, check the longform r&b mix from earlier in July. Excellent for chillin’ out in pretty much any context.
Last night, it was all Houston for Dummies from the Rub. I can’t figure how to link to individual podcasts, but just subscribe if you’re into it. Let me warn you now. Houston rap is not for people with delicate sensibilities. That ‘25 lighters’ hook sticks in my head for days tho… ‘I got to get paid.’
Filed under: audio, science | Tags: assemblies, CA1, captain funk, diana ross, hippocampus, ji, novelty, place cells, prospective, rate remapping, retrospective, trajectory, wilson
Ji and Wilson put out a paper a few months ago entitled “Firing Rate Dynamics in the Hippocampus Induced by Trajectory Learning.” I covered it in journal club and we had a lot of interesting discussion but couldn’t quite square the results and interpretation. Below I’ll lay out my thoughts on the paper. (more…)
Filed under: science | Tags: novelty, CA1, hippocampus, theta, ripples, phase precession, cheng, frank
We covered a paper from Loren Frank’s lab in journal club a few weeks ago. They looked at the coordination of neurons in the hippocampus as animals experienced a novel location. The hippocampus rapidly forms representations of new environments in the form of location-specific cell firing and these representations stabilize over a longer period. This paper examines some forms of neural coordination that may assist in stabilizing representations. The surprising result is that the important stabilizing events may occur during moments when the rat is replaying or thinking back over his experience in the novel location rather than while the rat is actively experiencing said location. (more…)
Filed under: science | Tags: cazala, gavello-baudy, medial septum, reinforcement
Muscimol, but not bicuculline, elicited and maintained self-administration when injected into the MSDB. The reinforcing properties of muscimol depended on the activation of local GABAA receptors in the MSDB and, secondarily, on a release of DA from the VTA and consecutive activation of D1 and D2/D3 dopaminergic receptors. These results suggest that MSDB-mediated reinforcement depends on the modulation of local GABAergic activity and the recruitment of the mesocorticolimbic DA system. - Gavello-Baudy et al 2008
Filed under: audio | Tags: drom, millenial territory orchestra, steven bernstein
Yo. Steven Bernstein’s Millenial Territory Orchestra is playing on Thursday at a new place in LES called Drom. It’s not free and I’m not rolling in dough right now, but it isn’t smart to miss these shows. MTO is an example of a band truly communicating and interacting on stage without noodly wankery. Cliches are avoided. Drums are not coddled. Eclectic influences abound. 15 bucks a ticket plus you gotta order food or two drink pushing your total price up to ~35. They win by providing really dope jazz and then making everybody smile with covers of Darling Nikki and Love is All You Need. I don’t particularly need to hear those again (though I’m fine with it) but it shows they aren’t trying to overbrow my uncultured ears.
Below the fold is the only full-length youtube I could find.
Filed under: science | Tags: 1988, antal, freund, GABA, hippocampus, medial septum, PHA-L
I’m studying the medial septum / diagonal band of Broca and its relation to hippocampus rhythms and firing patterns these days. Sometime soon I will have to do a deep lit review. Might as well get started.
Studies on this pathway apparently go back to the early 20th century. I think I can get some these early articles in print form. I’ll go back there when I get a chance. For now, I’ve been taking a look at early studies from Tamas Freund, who is now the director of the Institute of Experimental Medicine in Budapest and who had a string of important tracing studies over a little more than a decade of work.
I just want to document what I learn from each paper and when old ideas get turned over or improved. We’ll start with Freund and Antal 1988 in Nature. Three techniques are on display: Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L); immunohistochemical staining for parvalbumin and calbindin (two distinguishing markers for GABA-containing interneurons); and immunogold labeling for GABA itself.
I’m looking for indications of how phaseolus lectin transport works, but for now all you need to know is that when you inject this protein into the medial septum, it gets transported to the axon terminals. If you want to see how two brain areas are connected you inject PHA-L into the sending department and look for PHA-L in the receiving structure. Previous observations of PHAL-labeled axons from the medial septum indicated that projections could be broadly classified into two categories based on the appearance and targeting of the axon terminals. The important terminal type for this study appeared thicker at the end and formed ‘baskets’ around cell bodies in the hippocampus. Immunogold labeling indicated that these terminals contain GABA and are thus likely to be inhibitory to their targets. Who are they targeting though?
Co-staining with the GABAergic interneuron markers parvalbumin and calbindin showed that the major target for GABA transmission from the septum is inhibitory interneurons in the hippocampus, mainly in CA3 and dentate gyrus as opposed to CA1. There was no apparent preference for parv vs calbindin innervation and greater than 2/3 of all interneurons get some level of innervation.
It is especially nice that the authors note which layer within the hippocampal subfields are preferred for GABAergic innervation from the septum. Klausberger and Somogyi have got me thinking that I can use this as at least a heuristic for guessing which types of information are being affected. Cholinergic innervation is mainly aimed at proximal dendrites on principal (pyramidal or granule) cells in all subfields rather than distal apical tufts. In the CA fields this indicates that it should modulate information coming from within the hippocampal formation rather than projections from the entorhinal cortex. Not sure about the dentate yet. Freund and Antal don’t really break the molecular layer down like that.
GABAergic innervation prefers the interneuron somas and proximal dendrites in stratum oriens and stratum radiatum of the CA3 field and hilus and granule layers of the dentate gyrus. CA1 doesn’t receive nearly as much GABAergic innervation from the medial septum. Good to know.
This paper provides anatomical evidence that when GABAergic projection neurons in the septum are active, they should be disinhibiting to principal cells of the dentate gyrus and CA3 regions. I’m going to guess that this occurs in a rhythmic fashion and that the rhythm is in someway coordinated with the cholinergic output. More reading = more clarity.
P.S. Found more on how PHA-L works:
This lectin, Phaseolus vulgaris-leucoagglutinin (or phytohemagglutinin-L; PHA-L), is obtained from the red kidney bean and is best known for its mitogenic and leucocyte-agglutinating capacities. It has been assumed that the efficacy of PHA-L as an axonally transported marker derives from receptor-mediated endocytosis, but because lectin-glycoconjugate binding seems to require that binding sugars exist in complex, multiply branched forms, this has not yet been tested. - Sawchenko and Gerfen 1985
No word yet on if this limits the interpretation of PHA-L studies in any way.
Filed under: science | Tags: development, hippocampus, multipolar, nakahira, yuasa, migration
nakahira e16, originally uploaded by kaleidoscopikr.
The remarkable finding in the present study was the transient appearance of large numbers of EGFP-labeled multipolar cells in the SVZ and IMZ during E16-18. Their morphology has been described in the hippocampal primordium of the rabbit and monkey by the Golgi method, but their significance has not been adequately discussed. The presence of the multipolar cells in the SVZ and IMZ has also been reported in neocortical development. In our study, the multipolar cells accounted for 30.1% of the EGFP-labeled cells in the neocortical primordium of the mouse at E16. Their migratory pattern within the subcortical zone is nonradial and has been described as multipolar migration, as opposed to radial locomotion or somal translocation. The multipolar cells migrate slowly, at about one-fifth the rate of the bipolar cells in the neocortex. - nakahira and yuasa 2005
Filed under: audio, science | Tags: neocortex, cortical songs, ikegaya, yuste, thom yorke, nonclassical
Thom Yorke remixed a classical piece for a release called ‘Cortical Songs’. The title is intriguing and apparently refers to an orchestra partially controlled by a ‘tiny computer brain’. You can sample the result at imeem, courtesy of pitchfork media. Also, check out the record label’s myspace. They are called nonclassical music and they are repeat offenders in the classical remix department. I might pick up a few things from these guys.
Finally, here is an excerpt from the article, “Synfire Chains and Cortical Songs: Temporal Modules of Cortical Activity” by Ikegaya et al. 2004. Cortical songs seem to be motifs of neuronal activation patterns that can recur every few minutes or so.
the entire timespan in this picture is two minutes
Our data agree with the prediction that cortical activity flows through chains of synchronized neurons (synfire chains), which are reactivated with high temporal precision. Moreover, we describe a higher order grammar (18), by which these chains themselves can be modules of larger temporal structures (cortical songs), defined by their sequential order of activation, and which can last for minutes. These songs resemble spiking correlates of sequential behavior, like bird songs (19, 20) or spatial navigation (21), and have compressing dynamics, as if the circuit was replaying and modifying previously learned sequences (21–23). The mechanisms that generate and propagate synfire chains and cortical songs must be intrinsic to the cortical circuit, because they are preserved in slices, and might reflect the faithful reactivation of specific circuits (24), mediated by stereotypical synaptic dynamics (25, 26 ) and driven by pacemaker cells (8, 27). Because the activity drifts with time, it is also possible that short-lived patterns, perhaps reflecting ongoing circuit memory, are generated de novo (6, 28).
Filed under: science | Tags: spruston, diversity, identity, pyramidal, CA1, heterogeneity, somogyi, klausberger
Hippocampal pyramidal cells can be subcategorized based on several criteria besides anatomical location. For instance, distinct types have been described with relation to firing phase of gamma, change in firing rate during theta, tonic vs phasic firing patterns during theta, apical dendrite morphology, histological markers such as calbindin, and gene expression profiles.
I came across the calbindin distinction reading this recent review from Klausberger and Somogyi. They provided a few specimens in the supplementary info. It’s difficult to tell anything about their overall morphology though.
Not so for these beautiful babies from Spruston’s group. The apical dendrites are clearly either twinned or not. Unfortunately, the group wasn’t able to detect any clear functional difference between the two dendrite morphologies using whole cell recordings. I’m not terribly upset about that though. You might’ve even expected that dendrite morphology would have a lot more to do with network connectivity than intrinsic excitability.
There has been a lot of recent interest in the diversity of GABAergic interneurons throughout the cortex and including the hippocampus. Some folks recently characterized the most abundant (but relatively quiet) type of interneuron in the hippocampus, the Ivy Cell. PING came together and formed a new nomenclature for interneuron classification.
I dig that. We need to know about all the different types of interneurons and which parts of the circuit they act on and how they contribute to / are affected by system oscillations. OTOH, I’m into getting into a little more refined classification of pyramidal neurons. There is a lot less obvious diversity in this population. When we find differences, they are subtle. I think these are the types of neuronal properties that could be controlled by a manageable number of gene regulatory differences. What’s the difference between a phasic and a tonic Theta-ON cell? Is it perhaps expression of some small collection of ion channels or a GABA-A subunit? When we discover these precise single gene types of effects we can turn them back around on the system to allow investigation of the importance of a given physiological property. With combinatorial transgenic manipulations we should already have the capability to shut down firing of, say, Calbindin positive, CA1 pyramidal neurons. Then you can test for altered network properties, stimulus coding properties, and learning/navigation changes.
Anyway. I’m starting a collection of pyramidal pics on flickr. Gonna make me some mooooooo cards.
