Biology subjects

Haubrich, J.

Publications and source records attributed to Haubrich, J..

7 recordsLinked to original sources

bioRxiv2026

Strain- and age-dependent divergence in mouse appetitive spatial learning and decision strategies

Animals rely on associative spatial memory to navigate toward previously learned, reward-associated goals. This reward-guided navigation is supported by the hippocampus and its interactions with cortical and subcortical regions: processes which are vital for integrating sensory cues and forming experience-dependent associations. In adulthood, hippocampal-dependent information processing is shaped by aging, reflecting changes in synaptic plasticity and neuromodulatory support. In parallel, mice with distinct genetic backgrounds show systematic differences in behavior, sensory function, and hippocampal plasticity. How mouse strain and age interact to affect spatial appetitive memories has not been well defined. Here, we trained CBA/CaOlaHsd and C57BL/6 mice in early (2-3 months) or late adulthood (7-8 months), in daily training events, to perform a T-maze task with rewards available at a fixed location and decreasing probability in one maze arm. The task consisted of an initial deterministic phase in which a correct response was always rewarded, followed by a probabilistic phase during which reward omissions became increasingly prevalent. We measured correct choices, as well as latencies across training blocks, and combined trial-by-trial metrics with reinforcement learning modeling to assess decision strategies. We observed that CBA/CaOlaHsd mice displayed lower choice latencies than C57BL/6 mice, reached high performance earlier, and maintained better performance when the reward probability decreased. Age was associated with higher latencies and modulated both performance and decision policies in a strain-dependent manner. Moreover, CBA/CaOlaHsd mice displayed higher learning rates from positive outcomes and adopted strategies consistent with more robust context exploitation under uncertainty. C57BL/6 mice, by contrast, exhibited stronger omission-driven strategy switching. Together, these findings reveal robust strain- and age-dependent differences in trial-by-trial decision policies and spatial learning performance.

neuroscience↗

bioRxiv2025

β-adrenergic receptors modulate CA1 population coding during cumulative spatial memory formation and updating

Hippocampal neuronal ensembles are likely to support the acquisition, stabilization and updating of spatial experience. Spatial learning is typically cumulative, but little is known about how neuronal ensembles are manifested during this process. Here, we used wide-field Ca2+-imaging to monitor CA1 pyramidal cells during cumulative item-place learning in adult male CBA/CaOlaHsd mice. In control mice, initial learning prompted activity in a population of CA1 neurons, some of which re-appeared during re-exposure to the same item-place configuration 60 min after 1st exposure. Item-place reconfiguration (60 min later) caused a change in population dynamics as reflected by alterations in neuronal recruitment and reactivation patterns. Place cell-like properties, population burst activity, and functional connectivity were consistent with the encoding and updating of item-place memory. To examine the role of noradrenergic neuromodulation on these processes, we pharmacologically antagonized {beta}-adrenergic receptors({beta}-AR) prior to the 1st item-place exposure. This led to reduced cellular recruitment, disrupted ensemble reactivation, reduced spatial tuning, dampened population bursts, and altered functional connectivity within neurons. This was accompanied by impaired spatial learning compared to controls. Our results reveal the population activity of CA1 neurons during item-place learning and show that {beta}-AR support memory function by influencing both neuronal and network-level dynamics.

neuroscience↗

bioRxiv2025

Sparse memory ensembles set brain-wide network states to sustain learned associations

The ability to recall spatial memories and adapt behavior to changing conditions is essential for efficient navigation of environments. These processes are thought to rely on sparse populations of neurons, embedded within distributed brain networks. However, how the activity of these neurons impacts large-scale network connectivity to sustain behavior remains poorly understood. To address this, we tagged neurons active during peak performance in an appetitive spatial memory T-maze task in male and female TetTag-hM3Dq transgenic mice and chemogenetically reactivated these ensembles during functional magnetic imaging (fMRI) of brain activity. Reactivation of these ensembles triggered widespread network reorganization, optimizing the brain's modular specialization while maintaining integration across the network via key hubs and gateways. We identified two distinct clusters dominated by the ventral and dorsal hippocampus, respectively, that exhibit distinct connectivity with cortical and subcortical areas. Control mice showed effective extinction learning (EL) in the T-maze when the reward incentive was absent. Reactivating the tagged memory ensembles during EL significantly prevented this process. These findings reveal the brain-wide network hubs that support effective spatial memory acquisition, but also indicate that decay of this network connectivity is likely to be an essential facet of effective EL of spatial experience.

neuroscience↗

bioRxiv2023

Network-Level Changes in the Brain Underlie Fear Memory Intensity

The strength of a fear memory significantly influences whether it drives adaptive or maladaptive behavior in the future. Yet, how mild and strong fear memories differ in underlying biology is not well understood. We hypothesized that this distinction may not be exclusively the result of changes within specific brain regions, but rather the outcome of collective changes in connectivity across multiple regions within the neural network. To test this, rats were fear conditioned in protocols of varying intensities to generate mild or strong memories. Neuronal activation driven by recall was measured using c-fos immunohistochemistry in 12 brain regions implicated in fear learning and memory. The interregional coordinated brain activity was computed and graph-based functional networks were generated to compare how mild and strong fear memories differ at the systems level. Our results show that mild fear recall is supported by a well-connected brain network with small-world properties in which the amygdala is well-positioned to be modulated by other regions. In contrast, this connectivity is disrupted in strong fear memories and the amygdala is isolated from other regions. These findings indicate that the neural systems underlying mild and strong fear memories differ, with implications for understanding and treating disorders of fear dysregulation.

neuroscience↗

bioRxiv2022

Hippocampal β-adrenergic system modulates recognition memory reconsolidation

Targeting reconsolidation with propranolol, a blocker of {beta}-adrenergic receptors ({beta}-ARs), emerged as a potential treatment for maladaptive memories such as those involved in posttraumatic stress disorder (PTSD). Reconsolidation targeting treatments for PTSD are becoming a common practice in the clinic and it is important to unveil any side effects upon non-targeted memories. While previous studies have focused on propranolols effects on the reconsolidation of emotional/distressful memories, the present study asked whether propranolol is involved in the reconsolidation of recognition memories - by assessing its effects on distinct memory components and the role of the hippocampus. Rats performed an object recognition (OR) task where they were exposed to different objects: A and B presented during the sample phase; A and C presented during the reactivation phase; and D in combination of either A, B, or C during a final test. Intra-hippocampal injections of propranolol (5 {micro}g or 10 {micro}g) were conducted immediately after the reactivation session. Propranolol infusions consistently impaired the addition of novel information to the previously consolidated memory trace regardless of dose, and the retention of familiar objects was not affected. Higher doses of propranolol also hindered memory of a familiar object that was not presented during the reactivation session, but was previously placed at the same location where novel information was presented during reactivation. The present results shed light on the role of {beta}-ARs on the reconsolidation of different memory components and argue for the need for further studies examining possible recognition memory deficits following propranolol treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=66 SRC="FIGDIR/small/492176v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@69c9f9org.highwire.dtl.DTLVardef@14afbaborg.highwire.dtl.DTLVardef@1d0d0a2org.highwire.dtl.DTLVardef@314e0c_HPS_FORMAT_FIGEXP M_FIG C_FIG Post-traumatic stress disorder is a chronic mental health condition, which may develop following direct or indirect exposure to a traumatic event. The administration of propranolol to individuals affected by this disorder before the reactivation of the trauma-related memory may diminish the symptoms of this mental condition. Here, we show that such treatment may have effects on non-targeted memories, other than the fear/distressful memory. In a series of experiments in rodents, we show that intra-hippocampal infusion of propranolol immediately after recalling and updating a recognition memory trace hampers the reconsolidation of the initial recognition memory trace during recall. This may lead to difficulties in recalling recent events related to declarative memories. In a high dose, propranolol treatment may also affect the conjunctive component (association between multiple elements) of the memory trace - in addition to the effect on the elemental component. This may lead, for example, to difficulties in locating a parked car in a non-usual location after the post-stress traumatic stress disorder therapy with propranolol. HighlightsO_LIWe established the role of the hippocampal {beta}-adrenergic system in the reconsolidation of recognition memories. C_LIO_LIPropranolol treatment may impair the updating of recognition memory traces. C_LIO_LIHigh doses of propranolol may disrupt both elemental and conjunctive components of memory. C_LIO_LIClinical treatment with high doses of propranolol for post-traumatic stress disorder may unintentionally affect non-pathological components of memories. C_LI

pharmacology and toxicology↗

bioRxiv2022

Different conformations of EGF-induced receptor dimers involved in signaling and internalization

The structural basis of the activation of EGF receptors (EGFR) is still a matter of debate despite the importance of this target in cancer treatment. Whether agonists induce dimer formation or act on pre-formed dimers remain discussed. Here we provide direct evidence that EGFR activation results from EGF-induced dimer formation. This is well illustrated by i) a large increase in time resolved (TR)-FRET between snap-tagged EGFR subunits induced by agonists, ii) a similar effect of Erlotinib-related TK inhibitors despite the inactive state of the binding domain of the subunits, and iii) a similar TR-FRET efficacy in EGFR dimers stabilized by EGF or erlotinib with binding domains in active and inactive states, respectively. Surprisingly, TK inhibitors do not inhibit EGF-induced EGFR internalization despite their ability to fully block EGFR signaling. Only Erlotinib-related TK inhibitors promoting asymmetric dimers could slow down this process, while the lapatinib-related ones have almost no effect. These results reveal that the conformation of the intracellular TK dimer, rather than the known EGFR signaling is critical for EGFR internalization. These results also illustrate clear differences in the mode of action of TK inhibitors on the EGFR.

molecular biology↗

bioRxiv2020

Noradrenergic projections from the locus coeruleus to the amygdala constrain auditory fear memory reconsolidation

Memory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we extend the understanding of the mechanisms implicated in reconsolidation-resistant memories by investigating the hypothesis that specific modulatory signals shape memory formation into a state that lacks lability. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

neuroscience↗