14 research outputs found
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The neural circuit basis of learning
The astounding capacity for learning ranks among the nervous system’s most impressive features. This thesis comprises studies employing varied approaches to improve understanding, at the level of neural circuits, of the brain’s capacity for learning.
The first part of the thesis contains investigations of hippocampal circuitry – both theoretical work and experimental work in the mouse Mus musculus – as a model system for declarative memory. To begin, Chapter 2 presents a theory of hippocampal memory storage and retrieval that reflects nonlinear dendritic processing within hippocampal pyramidal neurons. As a prelude to the experimental work that comprises the remainder of this part, Chapter 3 describes an open source software platform that we have developed for analysis of data acquired with in vivo Ca2+ imaging, the main experimental technique used throughout the remainder of this part of the thesis. As a first application of this technique, Chapter 4 characterizes the content of signaling at synapses between GABAergic neurons of the medial septum and interneurons in stratum oriens of hippocampal area CA1. Chapter 5 then combines these techniques with optogenetic, pharmacogenetic, and pharmacological manipulations to uncover inhibitory circuit mechanisms underlying fear learning.
The second part of this thesis focuses on the cerebellum-like electrosensory lobe in the weakly electric mormyrid fish Gnathonemus petersii, as a model system for non-declarative memory. In Chapter 6, we study how short-duration EOD motor commands are recoded into a complex temporal basis in the granule cell layer, which can be used to cancel Purkinje-like cell firing to the longer duration and temporally varying EOD-driven sensory responses. In Chapter 7, we consider not only the temporal aspects of the granule cell code, but also the encoding of body position provided from proprioceptive and efference copy sources. Together these studies clarify how the cerebellum-like circuitry of the electrosensory lobe combines information of different forms and then uses this combined information to predict the complex dependence of sensory responses on body position and timing relative to electric organ discharge
The properties of mental experience evince its communicative function
The biological function of mental experience has remained enigmatic. Since conscious experiences are distinguished by their availability for verbal report, this work explores the hypothesis that mental experience functions in service of communication. By examining a system of communicating agents, I argue that agents with complex behavior and conflicting payoffs can benefit by influencing how they are perceived by others, and that this influence is achieved by communicating about the computational system controlling their behavior. It is impractical for biological or artificial computational systems to provide mechanistic models of themselves; instead, they can construct a mind: a simplifying — and sometimes misleading — model that accounts for behavior in terms of intentions, desires, goals, and emotions. Such a mind model can plausibly be implemented with typical neural mechanisms for computation and learning, and is remarkably consistent with human mental experience: a sparse and simplified account that prioritizes socially relevant information and distorts toward self-interest. The content of mental experience is proposed to be that which may be worth communicating about, and voluntary behaviors to be those whose motivations are worth communicating about. The social utility, feasibility of implementation, and consistency with mental experience together provide strong support for the hypothesis that the mind functions to communicate internal state
Place cell enrichment model data
Contains place cell data recorded during in vivo calcium imaging sessions of our goal-oriented learning task, as well as enrichment model parameters fit to the data, and saved simulations of the place cell enrichment model. Data is designed to be read by corresponding figure code at https://github.com/losonczylab/Zaremba_NatNeurosci_2017
Data from: Impaired hippocampal place cell dynamics in a mouse model of the 22q11.2 deletion
Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca2+ imaging in hippocampal area CA1 of wild-type and Df(16)A+/− mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A+/− mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction
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Dendritic Inhibition in the Hippocampus Supports Fear Learning
Fear memories guide adaptive behavior in contexts associated with aversive events. The hippocampus forms a neural representation of the context that predicts aversive events. Representations of context incorporate multisensory features of the environment, but must somehow exclude sensory features of the aversive event itself. We investigated this selectivity using cell type-specific imaging and inactivation in hippocampal area CA1 of behaving mice. Aversive stimuli activated CA1 dendrite-targeting interneurons via cholinergic input, leading to inhibition of pyramidal cell distal dendrites receiving aversive sensory excitation from the entorhinal cortex. Inactivating dendrite-targeting interneurons during aversive stimuli increased CA1 pyramidal cell population responses and prevented fear learning. We propose subcortical activation of dendritic inhibition as a mechanism for exclusion of aversive stimuli from hippocampal contextual representations during fear learning
Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding
Adult-born granule cells (abGCs) have been implicated in cognition and mood; however, it remains unknown how these cells behave in vivo. Here, we have used two-photon calcium imaging to monitor the activity of young abGCs in awake behaving mice. We find that young adult-born neurons fire at a higher rate in vivo but paradoxically exhibit less spatial tuning than their mature counterparts. When presented with different contexts, mature granule cells underwent robust remapping of their spatial representations, and the few spatially tuned adult-born cells remapped to a similar degree. We next used optogenetic silencing to confirm the direct involvement of abGCs in context encoding and discrimination, consistent with their proposed role in pattern separation. These results provide the first in vivo characterization of abGCs and reveal their participation in the encoding of novel information
Regulation of neuronal input transformations by tunable dendritic inhibition
Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type–specific pharmacogenetic silencing in vitro, we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons