Biology subjects

Schlecht, M.

Publications and source records attributed to Schlecht, M..

3 recordsLinked to original sources

bioRxiv2021

Dual projecting cells linking thalamic and cortical communication routes between the medial prefrontal cortex and hippocampus

The interactions between the medial prefrontal cortex (mPFC) and the hippocampus (HC) are critical for memory and decision making and have been specifically implicated in several neurological disorders including schizophrenia, epilepsy, frontotemporal dementia, and Alzheimers disease. The ventral midline thalamus (vmThal), and lateral entorhinal cortex and perirhinal cortex (LEC/PER) constitute major communication pathways that facilitate mPFC-HC interactions in memory. Although vmThal and LEC/PER circuits have been delineated separately we sought to determine whether these two regions share cell-specific inputs that could influence both routes simultaneously. To do this we used a dual fluorescent retrograde tracing approach using cholera toxin subunit-B (CTB-488 and CTB-594) with injections targeting vmThal and the LEC/PER in rats. Retrograde cell body labeling was examined in key regions of interest within the mPFC-HC system including: (1) mPFC, specifically anterior cingulate cortex (ACC), dorsal and ventral prelimbic cortex (dPL, vPL), and infralimbic cortex (IL); (2) medial and lateral septum (MS, LS); (3) subiculum (Sub) along the dorsal-ventral and proximal-distal axes; and (4) LEC and medial entorhinal cortex (MEC). Results showed that dual vmThal-LEC/PER-projecting cell populations are found in MS, vSub, and the shallow layers II/III of LEC and MEC. We did not find any dual projecting cells in mPFC or in the cornu ammonis (CA) subfields of the HC. Thus, mPFC and HC activity is sent to vmThal and LEC/PER via non-overlapping projection cell populations. Importantly, the dual projecting cell populations in MS, vSub, and EC are in a unique position to simultaneously influence both cortical and thalamic mPFC-HC pathways critical to memory. Significance StatementThe interactions between mPFC and HC are critical for learning and memory, and dysfunction within this circuit is implicated in various neurodegenerative and psychiatric diseases. mPFC-HC interactions are mediated through multiple communication pathways including a thalamic hub through the vmThal and a cortical hub through lateral entorhinal cortex and perirhinal cortex. Our data highlight newly identified dual projecting cell populations in the septum, Sub, and EC of the rat brain. These dual projecting cells may have the ability to modify the information flow within the mPFC-HC circuit through synchronous activity, and thus offer new cell-specific circuit targets for basic and translational studies in memory.

neuroscience↗

bioRxiv2019

'Awake delta' and theta-rhythmic hippocampal network modes during intermittent locomotor behaviors in the rat

Delta-frequency network activity is commonly associated with sleep or behavioral disengagement accompanied by a dearth of cortical spiking, but delta in awake behaving animals is not well understood. We show that hippocampal (HC) synchronization in the delta frequency band (1-4 Hz) is related to animals locomotor behavior using a detailed analysis of simultaneous head- and body-tracking data. In contrast to running-speed modulation of the theta rhythm (6-10 Hz, a critical mechanism in navigation models), we observed that strong delta synchronization occurred when animals were stationary or moving slowly and while theta and fast gamma (55-120 Hz) were weak. We next combined time-frequency decomposition of the local field potential with hierarchical clustering algorithms to categorize momentary estimations of the power spectral density (PSD) into putative modes of HC activity. Delta and theta power measures from these modes were notably orthogonal, and theta and delta coherences between HC recording sites were monotonically related to theta-delta ratios across modes. Next, we focused on bouts of precisely-defined running and stationary behavior. Extraction of delta and theta power density estimates for each instance of these bout types confirmed the orthogonality between frequency bands seen across modes. We found that delta-band and theta-band coherence within HC, and in a small sample, between HC and medial prefrontal cortex (mPFC), mirrored delta and theta components of the PSD. Delta-band synchronization often developed rapidly when animals paused briefly between runs, as well as appearing throughout longer stationary bouts. Taken together, our findings suggest that delta-dominated network modes (and corresponding mPFC-HC couplings) represent functionally-distinct circuit dynamics that are temporally and behaviorally interspersed amongst theta-dominated modes during navigation. As such these modes of mPFC-HC circuit dynamics could play a fundamental role in coordinating encoding and retrieval mechanisms or decision-making processes at a timescale that segments event sequences within behavioral episodes.

neuroscience↗

bioRxiv2018

Prefrontal pathways provide top down control of memory for sequences of events

We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, prelimbic cortex (PL) is positioned to influence sequence memory through extensive top down inputs to the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER), regions heavily interconnected with the hippocampus. Here, we tested the hypothesis that specific PLRE and PLPER projections regulate sequence memory retrieval using an hM4Di synaptic-silencing approach. First, we show that the suppression of PL activity impairs sequence memory. Second, we show that inhibiting PLRE and PLPER pathways effectively eliminated sequence memory. Last, we performed a sequential lag analysis showing that the PLRE pathway contributes to a working memory retrieval strategy, and the PLPER pathway contributes to a temporal context memory retrieval strategy. These results demonstrate that the PLRE and PLPER pathways serve as top down mechanisms that control sequence memory retrieval strategies.

neuroscience↗