hippocampal neurons

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

Amyloid-Beta Oligomers increases the amplitude and changes the firing pattern of spontaneous excitatory postsynaptic currents of hippocampal neurons in a model of Alzheimer’s disease

Describing the long-range trafficking dynamics of the AMPA receptors in hippocampal neurons using a quantitative model framework

Dysregulation of the cholesterol pathway alters epigenomic signatures of hippocampal neurons in Alzheimer’s Disease

Effect of antidepressant mirtazapine intake during gestation on the excitability of hippocampal neurons observed in the offspring

Effect of 3D synthetic microscaffold Nichoid on the morphology of hippocampal neurons

Formin-mediated actin filament regulation in the axon initial segment of hippocampal neurons

Hippocampal neurons sparsely code individual episodic memories in humans

Improved learning in adult mice with Pten gene depletion in hippocampal neurons

Insulin regulates GABAergic neurotransmission in hippocampal neurons in wild-type mice and a mouse model of Alzheimer's disease

Invisible killer: intracellular Aβ accumulation leads to endosomal/lysosomal leakage in hippocampal neurons

Iron chelation and ryanodine receptor inhibition protect primary hippocampal neurons against ferroptosis

Methamphetamine-induced remodelling of hippocampal neurons is orchestrated via cdc42 pathway

Novel insight into the neurodevelopmental disorder BBSOAS: Nr2f1 controls mitochondrial architecture in adult-born mouse hippocampal neurons

Probing subthreshold dynamics of hippocampal neurons by pulsed optogenetics

Pyk2 and MBD2 nuclear translocation and interaction in hippocampal neurons

Reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs

Regulation of NMDA receptor dynamics by brain-derived neurotrophic factor in hippocampal neurons

In vivo two-photon imaging of hippocampal neurons during the forced alternation working memory task in 5xFAD Alzheimer mouse model

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