Entorhinal cortex directs learning-related changes in CA1 representations
Grienberger C, Magee JC (2022) Nature. 611(7936):554-562
This work addresses the long-standing question of what neural mechanisms underlie learning within the mammalian brain. We show that a form of synaptic plasticity (BTSP) we discovered recently is responsible for the adaptive changes that occur in hippocampal area CA1 population activity as an animal learns a simple task. We also present evidence that the EC3 is the source of a target-like instructive signal that drives BTSP to achieve a desired CA1 population activity.
Inhibitory suppression of heterogeneously tuned excitation enhances spatial coding in CA1 place cells
Grienberger C, Milstein AD, Bittner KC, Romani S, Magee JC (2017) Nat Neurosci. 20(3):417-26
We showed that synaptic inhibition greatly contributes to the sparse structure of the CA1 place cell activity by controlling for the relatively broadly tuned excitation that CA1 receives from its afferent brain areas. In particular, the spatially localized fields of place cell firing (‘place fields’) emerge from the interaction of a localized increase in synaptic excitation with spatially uniform inhibition.
Behavioral time scale synaptic plasticity underlies CA1 place fields
Bittner KC, Milstein AD, Grienberger C, Romani S, Magee JC (2017) Science. 357, 1033-1036
We identified a new form of synaptic plasticity, called behavioral timescale synaptic plasticity (BTSP). This synaptic learning rule is driven by dendritic plateau potentials, with only a single plateau being sufficient to modify the strength of those synapses that are active in a seconds-long time window around the plateau. BTSP provides a mechanism for single-trial learning and could allow neurons to compute an association between an event and a delayed outcome, offering a solution to the long-standing ‘temporal credit assignment’ problem.
NMDA receptor-receptor dependent multidendrite Ca2+ spikes required for hippocampal burst firing in vivo
Grienberger C, Chen X, Konnerth A (2014). Neuron. 81(6):1274-81
We showed that a specific type of dendritic Ca2+ spike, Ca2+ plateau potentials (‘plateaus’ for short), underlies burst firing of CA1 neurons in vivo. These were the first simultaneous in vivo whole-cell and two-photon dendritic Ca2+ recordings in CA1 neurons.
*Preview article in Neuron by Thomas Oertner
Staged decline of neuronal function in vivo in an animal model of Alzheimer’s Disease
Grienberger C, Rochefort NL, Adelsberger H, Henning HA, Hill DN, Reichwald J, Staufenbiel M, Konnerth A. (2012). Nature Commun. 3:774
We showed that pyramidal cells in the visual cortex of mice that mimic the neuropathological and behavioral features observed in Alzheimer’s disease exhibit an altered input-output relationship. This work indicates that restoring this transformation to the baseline state pharmacologically might be beneficial for patients.
Sound-evoked network calcium transients in mouse auditory cortex in vivo
Grienberger C, Adelsberger H, Stroh A, Milos RI, Garaschuk O, Konnerth A. (2012). J Physiol. 590:899-918
We recorded population calcium signals in the auditory cortex of mice using fiber photometry. We found that these slow 1s - long sensory‐evoked network calcium transients (NCaT) are related to global ‘up states’ measured by electrocorticography and can be initiated by optogenetic activation of layer 5 pyramidal neurons, implying an intracortical mechanism for the initiation of the slow NCaTs.