There’s plenty of debate, but the classical view is that memory traces for events are laid down in cell ensembles across distributed hippocampal-cortical networks. Then the hippocampus is necessary, at least temporarily after encoding, for successful retrieval of these event memories via reinstatement of the patterns of activity within these cortical ensembles. According to this view, the hippocampus contains indices or pointers to cortical cell assemblies that collectively represent a given event. Observations of retrograde amnesia following hippocampal damage in human patients (such as H.M.), as well as in experimental animals, provide broad support for this view. However, they tell us little about how specific hippocampal and cortical cell ensembles interact to support memory retrieval. Two new studies (from Kazu Tanaka in the Wiltgen lab and Kiriana Cowansage in the Mayford lab) begin to shed light on this interaction. Both studies used a genetic strategy to tag active cells at the time of memory encoding with light-sensitive opsins and then optogenetically manipulate the activity of these ‘engram’ cells during retrieval.
These papers have just been published in Neuron. We were asked to write a commentary on these studies, and a pdf is available here.
We celebrated Liz’s cocaine paper last week with champagne and cake. In this study, Liz explored how rewarding things (in this case cocaine, not cake) become associated with particular places. Liz was able to show that a key population of neurons in the amygdala represent the association between a place and a reward, and that killing or silencing this population of cells effectively “erases” the drug memory. The paper is published in the Journal of Neuroscience. A pdf is available here.
Jerry Hogan is an emeritus professor in Psychology at the University of Toronto, and now is a visiting scholar at the University of Sao Paulo Institute for Advanced Studies. In his research career, Jerry studied animal behavior, and, in particular dust bathing in chicks (among other things). He’s been an important influence in the field of neuroethology, and because of this (and the fact that he’s reached a certain stage in his career…) the journal Behavioural Processes decided to do a special issue on his work. We were invited to contribute an article, and in this article we (actually Nathan Insel mainly) muse on what constitutes a mechanism in neuroscience research. Also, we were able to get Jerry, Aristotle and David Marr all in the same sentence. A pdf of the article is available here.
In September, we welcomed lots of new trainees to the lab. Bonny did her undergrad at Western and joins to do her MSc in Physiology. Lyn was an undergrad at York University and is a MA student in Psychology. Patrick did his MSc here at SickKids, and is now in the MD-PhD program in the Institute of Medical Sciences. Lina was an undergrad at U of T, and is now an MSC stduent in Physiology. Justin is a new postdoc, previously having worked at The University of Southampton in the UK. Thanks to Leo for portraiture.
Our paper on neurogenesis and forgetting is now featured in Science in the Classroom. This is an initiative led by Science magazine (in conjunction with the National Science Foundation) where they annotate research papers so that they can be used for teaching in highschools and universities. A huge thanks to Sarah Moore (at UCSD) and Katherine Akers for putting this together.
Top left, Tim Bussey waiting to speak at the Japanese Neuroscience meeting in Yokohama. Top right, Tom McHugh, Satoshi Kida and Seung-Hee Lee on the train to Ikebukuro. Bottom right, Jaideep Bains and Andrew Holmes at a standing Izakaya in Yokohama. Bottom left, Andrew Holmes and Josh Johansen on the Ikebukuro train. Last week there were a series of neuroscience meetings and events in and around Tokyo featuring Paul, Andrew Holmes, Brian Wiltgen, Bernard Balleine, Tim Bussey and Seung-Hee Lee. A big thanks to our hosts Tom McHugh, Josh Johansen and Satoshi Kida. More pictures posted at conferences >> 2014.
There’s a rich history of studies trying to understand how neural circuits form during development. While a large number of molecules play key roles in shaping circuits in the developing brain, one kinase (α-CaMKII) appears to play an especially important role. Studies from Holly Cline‘s lab in Xenopus showed that CaMKII fine tunes the integration of new cells into circuits. Taking inspiration from these studies we asked whether the role of α-CaMKII is conserved in the adult brain as newly generated granule cells integrate into the adult hippocampus. Maithe Arruda-Carvalho generated mice in which α-CaMKII could be deleted from newborn cells, and found that α-CaMKII-deficient cells developed abnormal morphology and poorer connections. Consistent with this, she found that these mice were impaired in forming hippocampus-dependent memories. Image above shows α-CaMKII (green) expression is restricted to mainly mature dentate granule cells (NeuN, red). Blue = DAPI. The paper is published in Journal of Neuroscience, and a pdf is available here.
In Washington this week telling the American Psychological Association all about Neurogenesis and Cognition were (from L to R): Tracey Shors, Liisa Galea, Paul, Mazen Kheirbek and Amar Sahay. Group selfie courtesy of Amar.
Memories are thought to be stored as enduring physical changes in ensembles of neurons, ensuring that activity patterns present at the time of encoding are recapitulated at the time of retrieval. But which neurons become part of this memory trace? Is allocation a random or non-random process? Our previous studies suggest the latter. In these studies we focused in particular on how fear memories are encoded in the amygdala. In our fear conditioning experiments, mice learn to associate a tone with a footshock and this association depends critically on neurons in the lateral amygdala (LA) . We found that manipulating the levels of the transcription factor cAMP responsive element binding (CREB) within this population of LA neurons influenced the likelihood of a neuron becoming part of a fear memory trace.
In this new study we explored the mechanisms underlying this CREB-mediated allocation. Previous studies had shown that one consequence of CREB over-expression is that cells become more excitable, and here we found that artificially increasing neuronal excitability produced exactly the same pattern of results as over-expressing CREB– more excitable neurons were more likely to become part of the memory trace. Moreover, co-expressing a factor that blocked these CREB-induced changes in excitability blocked these effects. Together these results suggest that relative levels of excitability determine which populations of cells encode the memory. The paper is published in Neuron, and Sheena and Adelaide explain all here: