The hippocampus contains rich oscillatory activity, with continuous ebbs and flows of rhythmic currents that constrain its ability to integrate inputs. During associative learning, the hippocampus must integrate inputs from a range of sources carrying information about events and the contexts in which they occur. Under these circumstances, temporal coordination of activity between sender and receiver is likely essential for successful communication. Previously, it has been shown that the coordination of rhythmic activity between the lateral entorhinal cortex (LEC) and the CA1 region of the hippocampus is tightly correlated with the onset of learning in an associative learning task. We aimed to examine whether rhythmic inputs from the LEC in specific frequency ranges were sufficient to enhance the temporal coordination of activity in downstream CA1. In urethane‐anesthetized rats, we applied extracellular low‐intensity alternating current stimulation across the length of the LEC. Using this method, we aimed to phase‐bias ongoing neuronal activity in LEC at a range of different frequencies (from 1.25 to 55 Hz). Rhythmic stimulation of LEC at both 35 and 50 Hz increased the proportion of CA1 neurons significantly entrained to the phase of the applied stimulation current. A subset of stimulation frequencies modified CA1 spiking relationships to the phase of local ongoing CA1 oscillations, with each stimulation frequency exerting a unique influence upon downstream CA1, often in frequency ranges outside the target stimulation frequency. These results suggest there are optimal frequencies for LEC–CA1 communication, and that different profiles of LEC rhythms likely have distinct outcomes upon CA1 processing.
Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner. Gamma perturbation disrupted the learning-induced assembly organization of target neurons. Our findings imply that pathway-specific gamma oscillations route task-relevant information between distinct neuronal subpopulations in the entorhinal-hippocampal circuit. We hypothesize that interregional gamma-time-scale spike coordination is a mechanism of neuronal communication.
more » « less- PAR ID:
- 10219984
- Publisher / Repository:
- American Association for the Advancement of Science (AAAS)
- Date Published:
- Journal Name:
- Science
- Volume:
- 372
- Issue:
- 6537
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- Article No. eabf3119
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
Abstract -
Klausberger, Thomas (Ed.)Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal–hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in Hippocampome.org . We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) and complemented the dataset with our own new data. By confronting the effect of brain state and recording methods, we highlight the equivalences and differences across conditions and offer a number of novel observations. We show how a heuristic approach based on oscillatory features of morphologically identified neurons can aid in classifying extracellular recordings of single cells and discuss future opportunities and challenges towards integrating single-cell phenotypes with circuit function.more » « less
-
Medial entorhinal cortex (MEC) supports a wide range of navigational and memory related behaviors. Well-known experimental results have revealed specialized cell types in MEC — e.g. grid, border, and head-direction cells — whose highly stereotypical response profiles are suggestive of the role they might play in sup- porting MEC functionality. However, the majority of MEC neurons do not exhibit stereotypical firing patterns. How should the response profiles of these more “het- erogeneous” cells be described, and how do they contribute to behavior? In this work, we took a computational approach to addressing these questions. We first performed a statistical analysis that shows that heterogeneous MEC cells are just as reliable in their response patterns as the more stereotypical cell types, suggest- ing that they have a coherent functional role. Next, we evaluated a spectrum of candidate models in terms of their ability to describe the response profiles of both stereotypical and heterogeneous MEC cells. We found that recently developed task-optimized neural network models are substantially better than traditional grid cell-centric models at matching most MEC neuronal response profiles — including those of grid cells themselves — despite not being explicitly trained for this pur- pose. Specific choices of network architecture (such as gated nonlinearities and an explicit intermediate place cell representation) have an important effect on the ability of the model to generalize to novel scenarios, with the best of these models closely approaching the noise ceiling of the data itself. We then performed in silico experiments on this model to address questions involving the relative functional relevance of various cell types, finding that heterogeneous cells are likely to be just as involved in downstream functional outcomes (such as path integration) as grid and border cells. Finally, inspired by recent data showing that, going beyond their spatial response selectivity, MEC cells are also responsive to non-spatial rewards, we introduce a new MEC model that performs reward-modulated path integration. We find that this unified model matches neural recordings across all variable-reward conditions. Taken together, our results point toward a conceptually principled goal-driven modeling approach for moving future experimental and computational efforts beyond overly-simplistic single-cell stereotypes.more » « less
-
Rubin, Jonathan (Ed.)Theta and gamma oscillations in the hippocampus have been hypothesized to play a role in the encoding and retrieval of memories. Recently, it was shown that an intrinsic fast gamma mechanism in medial entorhinal cortex can be recruited by optogenetic stimulation at theta frequencies, which can persist with fast excitatory synaptic transmission blocked, suggesting a contribution of interneuronal network gamma (ING). We calibrated the passive and active properties of a 100-neuron model network to capture the range of passive properties and frequency/current relationships of experimentally recorded PV+ neurons in the medial entorhinal cortex (mEC). The strength and probabilities of chemical and electrical synapses were also calibrated using paired recordings, as were the kinetics and short-term depression (STD) of the chemical synapses. Gap junctions that contribute a noticeable fraction of the input resistance were required for synchrony with hyperpolarizing inhibition; these networks exhibited theta-nested high frequency oscillations similar to the putative ING observed experimentally in the optogenetically-driven PV-ChR2 mice. With STD included in the model, the network desynchronized at frequencies above ~200 Hz, so for sufficiently strong drive, fast oscillations were only observed before the peak of the theta. Because hyperpolarizing synapses provide a synchronizing drive that contributes to robustness in the presence of heterogeneity, synchronization decreases as the hyperpolarizing inhibition becomes weaker. In contrast, networks with shunting inhibition required non-physiological levels of gap junctions to synchronize using conduction delays within the measured range.more » « less
-
Abstract Hippocampal network activity at theta frequencies (5-10Hz) is important for behavior. However, it remains unclear how behaviorally-relevant network theta rhythms arise and interact with cellular dynamics to dictate spike timing. We performed membrane voltage (Vm) imaging of individual CA1 pyramidal cells and parvalbumin interneurons with simultaneous local field potential (LFP) recordings in mice during locomotion. We found that Vm theta rhythms organize spike timing in both cell types regardless of behavioral conditions, but the Vm of parvalbumin interneurons is better synchronized with LFP. The temporal relationships between spikes and LFP theta reliably reflect the Vm-LFP relationships in parvalbumin cells, but not in pyramidal cells. Thus, cellular theta rhythms broadly organize spike timing in CA1 neurons, and parvalbumin interneurons are critical in coordinating network theta rhythms.
One-Sentence Summary Cellular membrane voltage of parvalbumin interneurons organizes spiking and network dynamics in the hippocampus.