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Abstract Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. The device tip can be miniaturized (as small as 50 µm) to minimize tissue damage while the ~20 times larger backend allows for industrial-scale connectorization. T-DOpE probes implanted in mouse hippocampus revealed canonical neuronal activity at the level of local field potentials (LFP) and neural spiking. Taking advantage of the triple-functionality of these probes, we monitored LFP while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity (optogenetics). Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit.
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NMDA receptors promote hippocampal sharp‐wave ripples and the associated coactivity of CA1 pyramidal cells
Abstract Hippocampal sharp‐wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during “offline” and sleep‐dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR‐associated activity remain unclear. Here, we combine biophysical modeling with in vivo local field potential (LFP) and unit recording to quantify changes in SWR dynamics following inactivation of NMDAR. In a biophysical model of CA3‐CA1 SWR activity, we find that NMDAR removal leads to reduced SWR density, but spares SWR properties such as duration, cell recruitment and ripple frequency. These predictions are confirmed by experiments in which NMDAR‐mediated transmission in rats was inhibited using three different NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of NMDAR‐mediated conductances also induced a reduction in the proportion of cell pairs that co‐activate significantly above chance across multiple events. Again, this prediction is corroborated by dorsal CA1 single‐unit recordings, where the NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are consistent with a framework in which NMDA receptors both promote activation of SWR events and organize SWR‐associated spiking content. This suggests that, while SWR are short‐lived events emerging in fast excitatory‐inhibitory networks, slower network components including NMDAR‐mediated currents contribute to ripple density and promote consistency in the spiking content across ripples, underpinning mechanisms for fine‐tuning of memory consolidation processes.
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- Award ID(s):
- 1724405
- PAR ID:
- 10455016
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Hippocampus
- Volume:
- 30
- Issue:
- 12
- ISSN:
- 1050-9631
- Page Range / eLocation ID:
- p. 1356-1370
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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