Biology subjects

Jarzebowski, P.

Publications and source records attributed to Jarzebowski, P..

5 recordsLinked to original sources

bioRxiv2026

Temporal Gating by Chandelier Cells Encodes Signed Prediction Errors

The brain refines its predictions of the world by updating its internal model whenever sensory input differs from expectation. The sign of this prediction error matters: an unexpected event signals that the model under-predicted (positive error), while a predicted event that fails to occur indicates that the model over-predicted (negative error), and the two should drive opposite synaptic changes. How cortical circuits represent error sign in spiking activity, and how that representation translates into synaptic learning, remain unresolved. We propose the Signed Error by Timing Asymmetry (SETA) model, in which the sign of a prediction error is encoded by when layer 2/3 neurons fire relative to a brief plasticity window in their layer 5 targets. Chandelier cells, an inhibitory cell type recruited by the prediction, impose a temporal clamp on layer 2/3 output: positive errors escape the clamp and arrive within the synaptic potentiation window, while negative errors are released only after the clamp decays and arrive later, during the synaptic depression window. The same circuit, therefore, biases downstream synapses toward either potentiation or depression depending on the prediction-error sign. We demonstrate this signed-error computation in a reduced two-compartment model, test SETA-specific predictions using in vivo recordings from mouse visual cortex, and examine how E/I imbalance leads to pathological consequences in predictive coding.

neuroscience↗

bioRxiv2025

Layer 1 NDNF interneurons form distinct subpopulations with opposite activation patterns during sleep in freely behaving mice

Non-rapid eye movement (NREM) sleep facilitates memory consolidation by transferring information from the hippocampus to the neocortex. Recent evidence suggests that this transfer occurs primarily when hippocampal sharp-wave ripples (SWRs) and thalamocortical spindles are synchronized. In this study, we asked what role cortical layer 1 NDNF-expressing (L1 NDNF) interneurons play during NREM sleep in gating information transfer during SWR-spindle synchronization. Using simultaneous cell-specific calcium imaging and local field potential recordings in freely moving mice, we discovered that L1 NDNF neurons form cell assemblies tuned to specific sleep stages, exhibiting differential responses to spindle synchronization. L1 NDNF neurons mediate slow inhibition through GABAB receptors. Systemic application of a GABAB receptor antagonist increased pyramidal neuron excitability during NREM sleep, enhanced inhibitory responses during SWRs, and disrupted SWR-spindle coupling. Overall, these findings suggest an important contribution of L1 NDNF neuron-mediated slow inhibition to the synchronization of sleep oscillations with potential implications for memory consolidation processes.

neuroscience↗

bioRxiv2022

Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs

A fundamental unresolved problem in neuroscience is how the brain associates in memory events that are separated in time. Here we propose that reactivation-induced synaptic plasticity can solve this problem. Previously, we reported that the reinforcement signal dopamine converts hippocampal spike timing-dependent depression into potentiation during continued synaptic activity (Brzosko et al., 2015). Here, we report that postsynaptic bursts in the presence of dopamine produces input-specific LTP in hippocampal synapses 10 minutes after they were primed with coincident pre- and postsynaptic activity. The priming activity sets an NMDAR-dependent silent eligibility trace which, through the cAMP-PKA cascade, is rapidly converted into protein synthesis-dependent synaptic potentiation, mediated by a signaling pathway distinct from that of conventional LTP. Incorporated into a computational model, this synaptic learning rule adds specificity to reinforcement learning by controlling memory allocation and enabling both instructive and supervised reinforcement learning. We predicted that this mechanism would make reactivated neurons activate more strongly and carry more spatial information than non-reactivated cells, which was confirmed in freely moving mice performing a reward-based navigation task.

neuroscience↗

bioRxiv2021

Different encoding of reward location in dorsal and ventral hippocampus

Hippocampal neurons encode a cognitive map for spatial navigation1. When they fire at specific locations in the environment, they are known as place cells2. In the dorsal hippocampus place cells accumulate at current navigational goals, such as learned reward locations3-6. In the intermediate-to-ventral hippocampus (here collectively referred to as ventral hippocampus), neurons fire across larger place fields7-10 and regulate reward- seeking behavior11-16, but little is known about their involvement in reward-directed navigation. Here, we compared the encoding of learned reward locations in the dorsal and ventral hippocampus during spatial navigation. We used calcium imaging with a head- mounted microscope to track the activity of CA1 cells over multiple days during which mice learned different reward locations. In dorsal CA1 (dCA1), the overall number of active place cells increased in anticipation of reward but the recruited cells changed with the reward location. In ventral CA1 (vCA1), the activity of the same cells anticipated the reward locations. Our results support a model in which the dCA1 cognitive map incorporates a changing population of cells to encode reward proximity through increased population activity, while the vCA1 provides a reward-predictive code in the activity of a specific subpopulation of cells. Both of these location-invariant codes persisted over time, and together they provide a dual hippocampal reward-location code, assisting goal- directed navigation17, 18.

neuroscience↗

bioRxiv2020

Cholinergic suppression of sharp wave-ripples impairs hippocampus-dependent spatial memory

The hippocampus plays a central role in long-term memory formation, and different hippocampal network states are thought to have different functions in this process. These network states are controlled by neuromodulatory inputs, including the cholinergic input from the medial septum. Here, we used optogenetic stimulation of septal cholinergic neurons to understand how cholinergic activity affects different stages of spatial memory formation in a reward-based navigation task in mice. We found that optogenetic stimulation of septal cholinergic neurons (1) impaired memory formation when activated at goal location but not during navigation; (2) reduced sharp wave-ripple (SWR) incidence at goal location; and (3) reduced SWR incidence and enhanced the-ta-gamma oscillations during sleep. These results underscore the importance of appropriate timing of cholinergic input in long-term memory formation, which might help explain the limited success of cholinesterase inhibitor drugs in treating memory impairment in Alzheimers disease.

neuroscience↗