Frontiers | Cholinergic modulation of cognitive processing: insights drawn from computational models | Frontiers in Behavioral Neuroscience

Frontiers | Cholinergic modulation of cognitive processing: insights drawn from computational models | Frontiers in Behavioral Neuroscience

Here is my newest paper.

In this review of cholinergic function we focus on the contributions that computational models have made to our understanding of the functional influences of acetylcholine.  I'm excited about it because it helps to illustrate how useful simulations of the physiological properties of neural networks can be helping to build our 'big picture' understandings.  At the highest level, our point is that such models serve to focus new research on the physiological mechanisms so as to most directly link them to the functional propoerties they have for psychology or systems neuroscience.  As I hope we've illustrated in this review, this has been particularly fruitful in the case of acetylcholine because of the multitude of effects cholinergic modulation has on neural network dynamics, many of which are seemingly contradictory in nature (simultaneously potentiating some synapses while depressing others).  As a reward, such modeling has shown, for example, that acetylcholine likely plays a central role in sculpting the focus of neural information processing and facilitating the encoding of novel associations.

I hope you enjoy and find it useful for i) understanding the role of modeling in holistic thinking; ii) understanding the potential roles of acetylcholine in cognitive processing; and iii) gaining insights into valuable next steps for empirical and computational explorations.

Choice of tetrode wire

Every detail seems to matter when it comes to getting good in-vivo recordings from awake behaving animals. One that I've been playing with in particular is the type of wire that I use to make my tetrodes. When I began, the lab standard was a stablohm wire from California Fine Wire. For all I knew, given that I was just learning to spin tetrodes and make my first recordings, this worked fine. Eventually, however, the spool ran out and we had to order more. We ordered what, based on the specs and supplier, should have been the identical stuff. It wasn't. The whole lab agreed, tetrodes made from the new wire were not as good. I even noticed the difference. My recordings were less stable from day to day and the overall lifespan of the implant, from a signal-to-noise stand point, was just worse.

Ultimately, we decided that the new wire was simply softer than what we had previously used. This manifested in soggy tetrodes that would be less likely to remain straight when turning down into the brain (resulting in instability over days). Further, it was difficult to get a good, clean final cut of the tetrodes. The wires would mush together instead of creating a nice four leaf clover pattern. These lumpy tips were more likely to short together during gold plating and may have been the reason why recordings would degrade over weeks instead of months or longer.

To solve the problem we switched to a new wire from a new supplier. After asking Amy Griffin what she uses in her lab, we switched to a chromium alloy supplied by Kanthal Palm Coast with the 'PAC 240' insulation. In contrast to the wire we replaced, this was much stronger thanks to the industrial grade insulation. The tetrodes were impressively stiff and the cuts seemed cleaner. The difficulty was, however, that the heating step in our tetrode making protocol, intended to fuse the wires together, simply didn't work. Additional heat or time helped (maximum heat, 6 passes at 6-10sec per pass) but didn't solve the problem. Finally, we found that asking Kanthal to coat the wire with 'Bond XTC', a heat activated bonding coating, made the best tetrodes we've seen to date.

The RO800 wire with PAC 240 insulation and Bond XTC coating tetrodes are incredibly stiff, cut very cleanly, and perform as well as I can ask for in the recording drives. I've had several animals with clear recordings for more than 8 months and have repeatedly stably isolated what I believe to be the same cells for weeks at a time.

On the down side - the use of these tetrodes with Axona Ltd. wire-wrap style 4-tetrode drives can be challenging. For exactly the same reason that these tetrodes are so stiff, they can be a real pain to wire wrap. The industrial insulation must be scrapped or burnt off - but because the wire contained within is not as strong it is frequently damaged in the process. Even if successfully exposed, the nichrome wire is not particularly maleable. For these drives, it is worth going with a whole different wire: platinum iridium. I'm sorry to say that I do not have the specs available for this wire at this point, I'll have to write about that wire in particular later.

All the best,

e