hippocampal neurons
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Are place cells just memory cells? Probably yes
Neurons in the rodent hippocampus appear to encode the position of the animal in physical space during movement. Individual ``place cells'' fire in restricted sub-regions of an environment, a feature often taken as evidence that the hippocampus encodes a map of space that subserves navigation. But these same neurons exhibit complex responses to many other variables that defy explanation by position alone, and the hippocampus is known to be more broadly critical for memory formation. Here we elaborate and test a theory of hippocampal coding which produces place cells as a general consequence of efficient memory coding. We constructed neural networks that actively exploit the correlations between memories in order to learn compressed representations of experience. Place cells readily emerged in the trained model, due to the correlations in sensory input between experiences at nearby locations. Notably, these properties were highly sensitive to the compressibility of the sensory environment, with place field size and population coding level in dynamic opposition to optimally encode the correlations between experiences. The effects of learning were also strongly biphasic: nearby locations are represented more similarly following training, while locations with intermediate similarity become increasingly decorrelated, both distance-dependent effects that scaled with the compressibility of the input features. Using virtual reality and 2-photon functional calcium imaging in head-fixed mice, we recorded the simultaneous activity of thousands of hippocampal neurons during virtual exploration to test these predictions. Varying the compressibility of sensory information in the environment produced systematic changes in place cell properties that reflected the changing input statistics, consistent with the theory. We similarly identified representational plasticity during learning, which produced a distance-dependent exchange between compression and pattern separation. These results motivate a more domain-general interpretation of hippocampal computation, one that is naturally compatible with earlier theories on the circuit's importance for episodic memory formation. Work done in collaboration with James Priestley, Lorenzo Posani, Marcus Benna, Attila Losonczy.
Chemogenetic therapies for epilepsy: promises and challenges
Expression of Gi-coupled designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. During my talk I will demonstrate that we obtained potent suppression of spontaneous epileptic seizures in mouse and a rat models for temporal lobe epilepsy using different DREADD ligands, up to one year after viral vector expression. The chemogenetic approach clearly outperforms the seizure-suppressing efficacy of currently existing anti-epileptic drugs. Besides the promises, I will also present some of the challenges associated with a potential chemogenetic therapy, including constitutive DREADD activity, tolerance effects, risk for toxicity, paradoxical excitatory effects in non-epileptic hippocampal tissue.
Effects of pathological Tau on hippocampal neuronal activity and spatial memory in ageing mice
The gradual accumulation of hyperphosphorylated forms of the Tau protein (pTau) in the human brain correlate with cognitive dysfunction and neurodegeneration. I will present our recent findings on the consequences of human pTau aggregation in the hippocampal formation of a mouse tauopathy model. We show that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to their neurodegeneration. In aged but not younger mice, pTau spreads to oligodendrocytes. During ‘goal-directed’ navigation, we detect fewer high-firing pyramidal cells, but coupling to network oscillations is maintained in the remaining cells. The firing patterns of individually recorded and labelled pyramidal and GABAergic neurons are similar in transgenic and non-transgenic mice, as are network oscillations, suggesting intact neuronal coordination. This is consistent with a lack of pTau in subcortical brain areas that provide rhythmic input to the cortex. Spatial memory tests reveal a reduction in short-term familiarity of spatial cues but unimpaired spatial working and reference memory. These results suggest that preserved subcortical network mechanisms compensate for the widespread pTau aggregation in the hippocampal formation. I will also briefly discuss ideas on the subcortical origins of spatial memory and the concept of the cortex as a monitoring device.
Rules for distributing synaptic weights in hippocampal neurons
Astrocytes contribute to remote memory formation by modulating hippocampal-cortical communication during learning
How is it that some memories fade in a day while others last forever? The formation of long-lasting (remote) memories depends on the coordinated activity between the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes, star-shaped glial cells, sense and modify neuronal activity, but their role in remote memory is scarcely explored. We manipulated the activity of hippocampal astrocytes during memory acquisition and discovered it impaired remote, but not recent, memory retrieval. We also revealed a massive recruitment of cortical-projecting hippocampal neurons during memory acquisition, a process that is specifically inhibited by astrocytic manipulation. Finally, we directly inhibited this projection during memory acquisition to prove its necessity for the formation of remote memory. Our findings reveal that the foundation of remote memory can be established during acquisition with projection-specific effect of astrocytes.
Multiple maps for navigation
Over the last several decades, the tractable response properties of parahippocampal neurons have provided a new access key to understanding the cognitive process of self-localization: the ability to know where you are currently located in space. Defined by functionally discrete response properties, neurons in the medial entorhinal cortex and hippocampus are proposed to provide the basis for an internal neural map of space, which enables animals to perform path-integration based spatial navigation and supports the formation of spatial memories. My lab focuses on understanding the mechanisms that generate this neural map of space and how this map is used to support behavior. In this talk, I’ll discuss how learning and experience shapes our internal neural maps of space to guide behavior.
Hippocampal replays appear after a single experience and slow down with subsequent experience as greater detail is incorporated
The hippocampus is implicated in memory formation, and neurons in the hippocampus take part in replay sequences, time-compressed reactivations of trajectories through space the animal has previously explored. These replay sequences have been proposed to be a form of memory for previously experienced places. I will present work exploring how these replays appear and change with experience. By recording from large ensembles of hippocampal neurons as rats explored novel and familiar linear tracks in various experiments, we found that hippocampal replays appear after a single experience and slow down with subsequent experience as greater detail is incorporated. We also investigated hover-and-jump dynamics within replays that are associated with the slow gamma (25-50Hz) oscillation in the LFP and found that replays slow down by adding more hover locations, corresponding to depiction of the behavioral trajectory with increased resolution. Thus, replays can reflect single experiences, and be rapidly modified by subsequent experience to incorporate more detail, consistent with their proposed role as a basic mechanism of hippocampally dependent memory.
Learning in abstract value spaces
Learning the consequences our choices have as we interact with our world is critical for flexible behavior. Relational knowledge of one’s environment gives structure to otherwise-individual one-to-one stimulus-outcome mappings, providing a substrate to globally update behavioral contingencies in the face of changes in the landscape of reward. In the brain, this relational knowledge is thought to be encoded in the hippocampus (HPC) in the form of a cognitive map, while prefrontal regions, such as orbitofrontal cortex (OFC), are thought to instantiate subjective estimates of location on the map, though direct neurophysiological evidence is lacking. In this talk, I will present recent work demonstrating the causal relationship between HPC and OFC as nonhuman primates perform a reward learning task requiring them to learn and maintain knowledge of changing stimulus-outcome associations. I will then provide direct evidence that single primate hippocampal neurons represent an abstract map of the value space defined by the task. Finally, I use behavioral modeling to highlight one possible strategy by which knowledge of value space is exploited by animals to detect changes in choice-outcome mappings and proactively update their behavior in response.
Human Hippocampal Neurons Represent Space and Reward Consistent with Successor Representation
COSYNE 2025
ATP6V1A is required for synaptic rearrangement and plasticity in murine hippocampal neurons
FENS Forum 2024
CAP2 overexpression in hippocampal neurons prevents actin abnormalities and cognitive defects in an Alzheimer’s disease model
FENS Forum 2024
Dynamics of postsynaptic densities in CA1 hippocampal neurons
FENS Forum 2024
Exploring the variability and functional implications of axon initial segment morphology in hippocampal neurons
FENS Forum 2024
Insulin action on the parameters of glutamatergic paired-pulse plasticity in cultured hippocampal neurons under hypoinsulinemia
FENS Forum 2024
KCC2a controls KCC2b membrane expression, recycling, and function in mature hippocampal neurons
FENS Forum 2024
Maternal consumption of a high-fat diet from pre-pregnancy to lactation impairs cognitive processes and inhibitory synaptic transmission of hippocampal neurons in mouse offspring
FENS Forum 2024
Modulation of CaV1.2 currents tunes dendritic growth in cultured hippocampal neurons
FENS Forum 2024
Region-specific morphological deficits of hippocampal neurons after postnatally induced reelin deficiency
FENS Forum 2024
DNA repair enzyme NEIL3 impacts the functionality of hippocampal neurons
FENS Forum 2024
Ryanodine receptors modulate synaptic transmission and non-L type calcium channels in mouse hippocampal neurons and adrenal chromaffin cells
FENS Forum 2024
Sex-dependent BDNF-mediated effects of Fingolimod on the architecture of mouse hippocampal neurons
FENS Forum 2024
Sub-toxic doses of glyphosate impair GABAergic synapses in cultured hippocampal neurons
FENS Forum 2024
Subcellular localization of the calcium channel Cav2.3 in cultured hippocampal neurons
FENS Forum 2024
Transcriptional response of primary hippocampal neurons following exposure to radiofrequency electromagnetic fields
FENS Forum 2024
Unconventional intracellular signaling pathway underlying cholinergic muscarinic receptor-induced axonal action potential threshold plasticity in hippocampal neurons
FENS Forum 2024
Upregulated extracellular matrix-related genes and impaired synaptic activity in dopaminergic and hippocampal neurons derived from Parkinson's disease patients with PINK1 and PRKN mutations
FENS Forum 2024
In vitro treatment of rat primary hippocampal neurons with 17-α-ethinyl estradiol shapes synaptic spines: molecular, morphological and functional effects
FENS Forum 2024
hippocampal neurons coverage
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