Biology subjects

Crestani, A. P.

Publications and source records attributed to Crestani, A. P..

5 recordsLinked to original sources

bioRxiv2026

Dopamine Release from the Locus Coeruleus Enables Temporal Binding in the Hippocampus

The hippocampus forms memories by associating events that are separated in time. These associations can be studied using trace conditioning, a procedure where a temporal gap is inserted between a conditional stimulus and an unconditional stimulus. Here, we examined how dopaminergic projections to CA1 support trace fear conditioning. Using fiber photometry and genetic lesions, we demonstrate that locus coeruleus (LC)-derived dopamine, rather than VTA input, is the primary source of dopamine in CA1 and is essential for trace learning. LC lesions reduced CA1 principal neuron activity and c-Fos expression. In-vivo imaging revealed that successful learning requires post-shock reactivation of stimulus-specific ensembles, a process compromised by LC lesions or long trace intervals. Finally, optogenetic stimulation of LC-CA1 projections during the post-shock period was sufficient to rescue learning in long-trace protocols. These findings identify LC-CA1 dopamine as a critical regulator of temporal binding via the facilitation of hippocampal memory trace reactivation.

animal behavior and cognition↗

bioRxiv2025

Single electrically induced epileptic afterdischarge triggers synaptic weakening, AMPA receptor endocytosis and shrinkage of dendritic spines in the hippocampus

Afterdischarge (AD) is an experimental model of electrically induced seizures. When induced in limbic structures, AD is known to induce acute behavioral alterations and flattening of local field potentials that persist for a few minutes. However, impairments in more complex cognitive processes such as learning and memory, can last for hours after the seizure. Considering the mismatch between ephemeral postictal electrophysiological changes and long-lasting cognitive impairments, synaptic plasticity emerges as a possible mechanism that integrates these findings. Therefore, we used a multilevel approach to evaluate the effects of a single seizure on synaptic plasticity. First, we showed that a single AD-eliciting stimulation at the perforant pathway-dentate gyrus (PP-DG) synapse causes long-lasting decrease of evoked postsynaptic potentials. Then, we observed that this functional alteration was accompanied by shrinkage of mushroom-shaped spines in the DG. Lastly, reduced levels of p(Ser845)-GluA1 and GluA1 subunits of AMPA receptors (AMPARs) were found in the hippocampal postsynaptic density. Together, our data suggest that a seizure induces a long-term depression (LTD)-like synaptic plasticity phenomenon, which is characterized by synaptic weakening, AMPAR endocytosis, and dendritic spines shrinkage. Furthermore, the postictal changes in synaptic plasticity observed here align with the course of cognitive impairments often reported in other studies.

neuroscience↗

bioRxiv2024

Multiple context discrimination in adult rats: sex variability and dynamics of time-dependent generalization of an aversive memory

Memory generalization involves the transfer of conditioned fear responses to novel contexts, a phenomenon observed in systems consolidation, whereby a time-dependent reduction in discrimination precision occurs due to the reorganization of brain regions supporting memory retrieval. To understand the fine temporal structure of this process across sexes, young adult female and male rats were trained in contextual fear conditioning and tested in the same or one of three distinct novel contexts at 2, 28 or 45 days post-training. Neutral contexts were designed to allow graded levels of fear expression relative to the training context, and sex differences were evident at the recent memory test. This pattern, however, disappeared over time due to partial generalization, with fear converging into similar, higher values, grouped into two levels for both sexes. In all experiments, females were better discriminators and displayed lower fear responses than males, apparently prioritizing different sensory modalities, with multivariate analysis suggesting that chamber size was salient for females and floor texture for males. This study is the first to compare fear responses between adult female and male rats across multiple neutral contexts and timepoints revealing several dimorphic findings.

neuroscience↗

bioRxiv2023

Cell type-specific representation of spatial context in the rat prefrontal cortex

The ability to represent ones own position in relation to cues, goals, or threats is crucial to successful goal-directed behavior. Using transgenic rats expressing Cre recombinase in parvalbumin (PV) neurons (PV-Cre rats) we demonstrate cell type-specific encoding of spatial and movement variables in the medial prefrontal cortex (mPFC) during reward foraging. Single neurons encoded the conjunction of the animals spatial position and the location of the reward, referred to as the spatial context. The spatial context was most prominently represented by the inhibitory PV interneurons. Movement towards the reward was signified by increased local field potential (LFP) oscillations in the gamma band but this LFP signature was not related to the spatial information in the neuronal firing. The results highlight how spatial information is incorporated into cognitive operations in the mPFC. The presented PV-Cre line opens for expanded research approaches in rats.

neuroscience↗

bioRxiv2020

Time-course of systems consolidation and fear memory generalization in adolescent rats of different sex

Generalization is an adaptive process that allows animals to deal with threatening circumstances similar to prior experiences. Systems consolidation is a time-dependent process in which memory loses it precision concomitantly with reorganizational changes in the brain structures that support memory retrieval. In this, memory becomes progressively independent from the hippocampus and more reliant on cortical structures. Generalization, however, may take place much faster in adult animals depending on the presence of sex hormones. Notwithstanding its relevance, there are few studies on sex differences in memory modulation. Here, a contextual fear discrimination task was used to investigate the onset of memory generalization and hippocampus-independence in adolescent male and female rats (P42-49). Subjects were tested 2, 7, 14, 21 or 28 days after training, with females showing memory generalization from day 21 on, whereas males surprisingly unable to discriminate contexts at any time. Ovariectomized females, however, displayed an early onset of generalization. Consistently, pre-test pharmacological blocking of dorsal hippocampus was able to impair memory retrieval in females, but not in males, which indicate that precise memory is dependent on the hippocampus. To our notice, this is the first report of a memory systems consolidation process - expressed in its two dimensions, neuroanatomical and qualitative - in adolescent female rats, and one that can also be accelerated by the reduction of sex hormones through ovariectomy. It is also unprecedented that despite adolescent male rats being able to remember fear learning, they did not discriminate contexts with any precision.

neuroscience↗