bioRxiv Science⌕ Search

Biology subjects

Dorian, C. C.

Publications and source records attributed to Dorian, C. C..

3 recordsLinked to original sources

Hippocampal sequences represent working memory and implicit timing

Working memory (WM) and timing are considered distinct cognitive functions, yet the neural signatures underlying both can be similar. To address the hypothesis that WM and timing may be multiplexed we developed a novel rodent task where 1st odor identity predicts the delay duration. We found that WM performance decreased when delay expectations were violated. Performance was worse for unexpected long delays than for unexpected short delays, suggesting that WM may be tuned to expire in a delay-dependent manner. Calcium imaging of dorsal CA1 neurons revealed odor-specific sequential activity tiling the short and long delays. Neural sequence structure also reflected expectation of the timing of the 2nd odor--i.e., of the expected delay. Consistent with the hypothesis that WM and timing may be multiplexed, our findings suggest that neural sequences in dorsal CA1 may encode cues and cue-specific elapsed time during the delay period of a WM task.

neuroscience↗

Non-spatial hippocampal behavioral timescale synaptic plasticity during working memory is gated by entorhinal inputs

Behavioral timescale synaptic plasticity (BTSP) is a form of synaptic potentiation where a single plateau potential in hippocampal neurons forms a place field during spatial learning. We asked whether BTSP can also form non-spatial responses in the hippocampus and what roles the medial and lateral entorhinal cortex (MEC and LEC) play in driving non-spatial BTSP. Two-photon calcium imaging of dorsal CA1 neurons while mice performed an odor-cued working memory task revealed plateau-like events which formed stable odor-specific responses. These BTSP-like events were much more frequent during the first day of task learning, suggesting that BTSP may be important for early learning. Strong single-neuron stimulation through holographic optogenetics induced plateau-like events and subsequent odor-fields, causally linking BTSP with non-spatial representations. MEC chemogenetic inhibition reduced the frequency of plateau-like events, whereas LEC inhibition reduced potentiation and field-induction probability. Calcium imaging of LEC and MEC temporammonic CA1 projections revealed that MEC axons were more strongly activated by odor presentations, while LEC axons were more odor-selective, further confirming the role of MEC in driving plateau-like events and LEC in relaying odor-specific information. Altogether, odor-specific information from LEC and strong odor-timed activity from MEC are crucial for driving BTSP in CA1, which is a synaptic plasticity mechanism for generation of both spatial and non-spatial responses in the hippocampus.

neuroscience↗

Open-source, high performance miniature multiphoton microscopy systems for freely behaving animals

Here we describe the development of the UCLA 2P Miniscope, an easily adopted, open-source miniature 2-photon microscope capable of recording calcium dynamics from neurons located in deep structures and in dendrites over a 445 m x 380 m field of view (FOV) during free behavior. The system weighs approximately 4g and utilizes two on-board silicon-based photon detectors for highly sensitive measurements. All hardware is designed for high performance and ease of assembly, while minimizing cost. To test the 2P miniature microscope, we recorded in three experimental conditions to highlight its capabilities during free behavior in mice. First, we recorded calcium dynamics from place cells in hippocampal area CA1. Next, we resolved calcium transients from dendrites in retrosplenial cortex during 30 minutes of free behavior. Last, we recorded dentate granule cell activity at a depth of over 620 m, through an intact hippocampal CA1 during an open field behavior. The dentate granule cell recordings, to our knowledge, are the first optical recordings from these neurons ever performed in the intact hippocampus during free behavior. The miniature microscope itself and all supporting equipment are open-source and all files needed for building the scope can be accessed through the UCLA Golshani Lab GitHub repository.

neuroscience↗