Biology subjects

Schlingloff, D.

Publications and source records attributed to Schlingloff, D..

5 recordsLinked to original sources

bioRxiv2026

Hippocampo-septal inhibitory feedback controls the medial septal circuit as a function of brain state, pyramidal cell activity and movement speed.

Encoding novel experiences and retrieving stored information rely on the hippocampal theta rhythm in several mammalian species. Coordination of putative pacemakers in the medial septum (MS) by the GABAergic hippocampo-septal (HS) feedback is hypothesized to be essential for theta genesis. In order to reveal how the HS-feedback controls the MS circuit, and through it hippocampal oscillations in general, we set out to uncover the behavior-related activity of HS neurons as well as how different components of the MS network are regulated by the HS-feedback. Utilizing computational modelling and in vivo optogenetic manipulation of the HS pathway, we show that the HS feedback is not required for theta generation, which is primarily governed by intra-MS connections. HS blockade did not alter the phase coupling of MS neurons to hippocampal theta rhythm nor the synchrony between rhythmic MS neurons but augmented ongoing theta and coupled mid-gamma oscillations in the hippocampus. By contrast, correlated activity between non-rhythmic MS neurons was sensitive to HS blockade. Moreover, the HS feedback scaled with hippocampal activity and running speed. In turn, modulation of MS neurons by running and ripples was diminished by the transient suppression of HS terminals. These findings suggest that the HS feedback exerts inhibitory control of the MS depending upon hippocampal output and movement speed.

neuroscience↗

bioRxiv2026

Cholinergic--dopaminergic interplay underlies prediction error broadcasting

Neuromodulatory systems, notably basal forebrain cholinergic and midbrain dopaminergic pathways, critically influence reinforcement learning 1-3. However, whether and how they cooperate or compete to jointly control associative learning functions remains unresolved. Here we demonstrate that basal forebrain cholinergic and midbrain dopaminergic projection systems form a coordinated and cross-regulating architecture for encoding prediction errors. Using dual-cell-type optogenetic tagging and real-time neurotransmitter measurements in mice performing a psychometric operant learning task, we simultaneously monitored cholinergic and dopaminergic activity during learning. Dopamine and acetylcholine jointly encoded reward prediction errors synergistically following reward and reward-predicting stimuli. In contrast, aversive outcomes elicited opposite responses in cholinergic neurons and approximately half of dopaminergic neurons. Activity in these two populations exhibited negative trial-by-trial correlations, revealing antagonistic dynamics. Consistently, channelrhodopsin-assisted circuit mapping uncovered a disynaptic inhibitory pathway from cholinergic to dopaminergic neurons. Chemogenetic suppression of cholinergic activity disrupted dopaminergic prediction error signaling, reduced punishment-induced suppression of dopamine release, and impaired learning. These results demonstrate that prediction error signaling is jointly implemented by coordinated interactions between major neuromodulatory systems, challenging the prevailing view of their functional independence and revealing coordinated cross-system interactions as an organizing principle of reinforcement learning, with implications for neuropsychiatric disease 4-6.

neuroscience↗

bioRxiv2025

Most ventral pallidal cholinergic neurons are cortically projecting bursting basal forebrain cholinergic neurons

The ventral pallidum (VP) lies at the intersection of basal ganglia and basal forebrain circuitry, possessing attributes of both major subcortical systems. Basal forebrain cholinergic neurons are rapidly recruited by reinforcement feedback and project to cortical and subcortical forebrain targets; in contrast, striatal cholinergic cells are local interneurons exhibiting classical pause-burst responses to rewards. However, VP cholinergic neurons (VPCNs) are less characterized, and it is unclear whether basal forebrain and striatal type cholinergic neurons mix in the VP. Therefore, we performed anterograde and mono-transsynaptic retrograde labeling, in vitro acute slice recordings and bulk calcium recordings of VPCNs. We found that VPCNs broadly interact with the affective circuitry that processes rewards and punishments, targeting the basolateral amygdala, the nucleus accumbens, the medial prefrontal cortex and the lateral habenula, while receiving inputs from the nucleus accumbens, hypothalamus, central amygdala, bed nucleus of stria terminalis and the ventral tegmental area. Bulk calcium recordings revealed VPCN responses to rewards, punishments and reward-predicting cues, like those of the horizontal diagonal band of Broca of the basal forebrain. Acute slice recordings showed that most VPCNs resembled the bursting type of basal forebrain cholinergic neurons (BFCNs), while a few of them were of the regular rhythmic type, which sharply differentiated most VPCNs from striatal cholinergic interneurons. These results were confirmed by in vivo electrophysiological recordings of putative VPCNs largely resembling bursting BFCNs. We conclude that most VPCNs are BFCNs with specialized connectivity to relay aversive and appetitive stimuli to the reinforcement circuitry, possibly implicated in mood disorders and addiction.

neuroscience↗

bioRxiv2019

Distinct synchronization, cortical coupling and behavioural function of basal forebrain cholinergic neuron types

Basal forebrain cholinergic neurons (BFCN) densely innervate the forebrain and modulate synaptic plasticity, cortical processing, brain states and oscillations. However, little is known about the functional diversity of cholinergic neurons and whether distinct types support different functions. To examine this question we recorded BFCN in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCN that markedly differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (BFCNBURST) fired in zero-lag synchrony with each other, phase-locked to cortical theta activity and fired precisely timed bursts of action potentials after reward and punishment. Regular firing cholinergic neurons (BFCNREG) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity (5-10 Hz), fired asynchronously with each other and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of BFCNBURST neurons to auditory cortex predicted the timing of mouse responses, whereas tone-evoked cortical coupling of BFCNREG predicted correct detections. We propose that cortical activation relevant for behavior is controlled by the balance of two cholinergic cell types, where the precise proportion of the strongly activating BFCNBURST follows an anatomical gradient along the antero-posterior axis of the basal forebrain.

neuroscience↗

bioRxiv2017

Synaptic co-transmission of acetylcholine and GABA regulates hippocampal states

The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter, acetylcholine. Yet, using immune-electron tomographic, molecular anatomical, optogenetic and physiological techniques, we find that mouse hippocampal cholinergic terminals invariably establish synapses and their vesicles dock at synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes fast composite postsynaptic potentials, which are mutually cross-regulated by presynaptic auto-receptors and display different short-term plasticity. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. The synaptic nature of the forebrain cholinergic system with differentially regulated, fast, GABAergic and cholinergic co-transmission suggests a hitherto unrecognized level of synaptic control over cortical states. This novel model of hippocampal cholinergic neurotransmission could form the basis for alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders.\n\nSupplementary materials are attached after the main text.

neuroscience↗