Biology subjects

Marin-Burgin, A.

Publications and source records attributed to Marin-Burgin, A..

6 recordsLinked to original sources

bioRxiv2026

Tau isoforms modulate the axon initial segment controlling axonal trafficking and neuronal excitability

The axon initial segment (AIS) is a specialized neuronal compartment integrating action potential initiation with selective control of axonal trafficking. The microtubule associated protein tau is a central regulator of cytoskeletal organization and transport, yet how distinct tau isoforms contribute to AIS development and function remains unclear. Here, we examined the role of tau isoform relative abundance in regulating AIS establishment, maturation, excitability, and transport selectivity using murine primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons combined with super resolution imaging, electrophysiology, and live trafficking assays. We found that tau expression levels and isoform content modulate the timing and robustness of AIS maturation. In murine neurons, tau deficiency or predominance of 3 repeat (3R) tau delays Ankyrin G accumulation and AIS stabilization without preventing AIS formation. hiPSC-derived neurons display an intrinsic AIS developmental program accompanied by progressive changes in tau isoform content. Super resolution DNA PAINT reveals that endogenous tau decorates axonal microtubules in discrete nanoclusters with compartment specific distributions. Modulation of the endogenous 3R/4R tau balance in hiPSC-derived neurons shows that isoform composition, independently of tau levels, regulates AIS positioning and Ankyrin G organization. Functionally, shifts towards 3R-tau reduce sodium currents, impair action potential firing, and alter lysosomal transport dynamics within the AIS. Together, these findings identify tau isoform balance as a developmental regulator of AIS maturation, linking cytoskeletal organization to neuronal excitability and transport gating. Because the aberrant alternative tau splicing of exon 10 is a defining feature of primary tauopathies, our results provide mechanistic insight into how imbalanced tau isoforms may contribute to neuronal dysfunction.

cell biology↗

bioRxiv2025

Neuronal development shapes activity-dependent gene expression in a stimulus-specific manner

Neuronal activity-dependent gene expression is fundamental to a wide variety of brain functions. However, how development progress and stimulation modalities specifically affect neuron transcription is not fully understood. In this work, we first investigate the influence of development on neuronal firing and activity-driven transcription. We used an RNA sequencing approach over 7 days in vitro (DIV) or mature 21 DIV neurons, comparing neuronal depolarization with potassium chloride (KCl) versus Biccuculine application, a synaptic modality to induce neuronal activity. To further investigate how different activity patterns influence gene transcription in mature neurons, we compared global gene expression in neurons treated with three different and extensively used activation protocols: KCl, Bicuculine (Bic), and TTX withdrawal (TTXw). Our results demonstrate a strong influence of development on activity-dependent gene expression, and showed that different patterns of neuronal activity induce different transcriptional profiles and exhibit distinct temporal dynamics for the same genes. These findings offer novel insights into the complex relationship between neuronal activity and gene expression, shedding light on the context-dependent nature of activity-dependent transcriptional responses.

neuroscience↗

bioRxiv2024

Lateral entorhinal cortex afferents reconfigure the activity in piriform cortex circuits

Odours are key signals for guiding spatial behaviours such as foraging and navigation in rodents. It has recently been found that odour representations in the piriform cortex (PCx) can also contain information about their spatial context. However, the precise origins of this information within the brain and its subsequent integration into the microcircuitry of the PCx remains unknown. In this study, we focus on the lateral entorhinal cortex (LEC) as a candidate for carrying spatial contextual information to the PCx, to investigate how it affects the PCx microcircuit and its response to olfactory inputs. Utilising mice brain slices, we performed patch clamp recordings targeting both superficial (SP) and deep (DP) pyramidal neurons, as well as parvalbumin (PV) and somatostatin (SOM) inhibitory interneurons. Concurrently, we optogenetically stimulated excitatory LEC projections to study their impact on PCx activity. We found that LEC inputs are heterogeneously distributed in the PCx microcircuit, evoking larger excitatory currents in SP and PV neurons compared to DP and SOM neurons, respectively, due to their higher monosynaptic connectivity. Moreover, LEC inputs exert a differential effect on the inhibitory circuits, activating PV while suppressing SOM interneurons. We further studied the interaction among LEC inputs and the sensory afferent signals originating from the lateral olfactory tract (LOT) onto the PCx. Our findings demonstrated that both SP and DP neurons show a general increase in their spiking response when LEC and LOT are simultaneously activated. Notably, DP neurons exhibit a sharpening of their response attributable to LEC-induced inhibition that effectively suppresses the delayed spikes evoked by LOT stimulation. These observations suggest a regulatory mechanism whereby LEC inputs inhibit recurrent activity by activating PV interneurons. Our results show that LEC afferents reconfigure PCx activity and contribute to the understanding of how odour objects are formed within the PCx integrating both olfactory and contextual information. Significant statementPrimary sensory cortices are more complex than initially thought, encoding movement-related information, as well as spatial maps of animal location. The primary olfactory cortex, the piriform cortex (PCx), not only responds to the presence of odours, but to other non-olfactory signals like the spatial context in which odours are presented. The source of the contextual modulation is not known. In this work, we studied the modulation of PCx neurons by afferents arriving from the lateral entorhinal cortex (LEC), an area related to spatial representation. By the use of optogenetic to activate LEC inputs we found that its activation recruits excitatory and inhibitory circuits in PCx. The interaction of LEC inputs with afferents carrying odour information arriving from the lateral olfactory tract (LOT) resulted in a sharpening PCx principal neurons response to LOT, by a reduction in recurrent activity through PV interneurons. This circuital reorganisation of activity in PCx by LEC afferents could be an important mechanism to switch responses to be favouring dominance of the LOT pathway over the recurrent pathway. These results shed light on the understanding of how contextual aspects of animal experience, in which LEC is involved, can influence odour processing potentially leading to a richer representation of odour objects.

neuroscience↗

bioRxiv2023

Acquisition of non-olfactory encoding improves odour discrimination in olfactory cortex

Primary sensory cortices, initially considered elementary encoders of physicochemical attributes of environmental stimuli, are now known to be modulated by other aspects of experience, such as attentional state and internal expectations 1-3, movement-related signals 4-7 and spatial information 2, 8, 9. However, the specific role of these signals in cortical sensory processing is not fully understood 10. Here we reveal multiple and diverse non-olfactory responses in the primary olfactory (piriform) cortex (PCx), which dynamically enhance PCx odour discrimination according to behavioural demands. We designed a behavioural task using a virtual reality environment and performed recordings in PCx neurons. In this task, mice were trained to associate specific odours with visual contexts in order to receive a reward. We found that learning shifts PCx activity from encoding solely odour identity to a more complex regime. In this regime, positional, contextual, and associative responses emerge on odour-responsive neurons that thus become mixed-selective. Contextual information is sustained in PCx activity of expert animals, specifically when visual context identity is needed to solve the task. After learning, odours are better decoded from PCx activity when mice are engaged in the task and when odours are presented within a rewarded context. This enhancement of PCx olfactory processing is reliant on the acquired mixed-selectivity. Thus, the integration of extra-sensory inputs within primary sensory cortices can encode the behavioural relevance of encountered stimuli while improving sensory processing.

neuroscience↗

bioRxiv2022

Adult-born granule cells improve stimulus encoding and discrimination in the dentate gyrus

Heterogeneity plays an important role in diversifying neural responses to support brain function. Adult neurogenesis provides the dentate gyrus with a heterogeneous population of granule cells (GCs) that were born and developed their properties at different times. Immature GCs have distinct intrinsic and synaptic properties than mature GCs and are needed for correct encoding and discrimination in spatial tasks. How immature GCs enhance the encoding of information to support these functions is not well understood. Here, we record the responses to fluctuating current injections of GCs of different ages to study how they encode stimuli. Immature GCs produce unreliable responses compared to mature GCs, exhibiting imprecise spike timings across repeated stimulation. We use a statistical model to describe the stimulus-response transformation performed by GCs of different ages. We fit this model to the data and obtain parameters that capture GCs encoding properties. Parameter values from this fit reflect the maturational differences of the population and indicate that immature GCs perform a differential encoding of stimuli. To study how this age heterogeneity influences encoding by a population, we perform stimulus decoding using populations that contain GCs of different ages. We find that, despite their individual unreliability, immature GCs enhance the fidelity of the signal encoded by the population and improve the discrimination of similar time dependent stimuli. Thus, the observed heterogeneity confers the population with enhanced encoding capabilities.

neuroscience↗

bioRxiv2019

Cholinergic modulation of dentate gyrus processing through dynamic reconfiguration of inhibitory circuits

The dentate gyrus (DG) of the hippocampus plays a key role in memory formation and it is known to be modulated by septal projections. By performing electrophysiology and optogenetics we evaluated the role of cholinergic modulation in the processing of afferent inputs in the DG. We showed that mature granule cells (GCs), but not adult-born immature neurons, have increased responses to afferent perforant path stimuli upon cholinergic modulation. This is due to a highly precise reconfiguration of inhibitory circuits, differentially affecting Parvalbumin and Somatostatin interneurons, resulting in a nicotinic-dependent perisomatic disinhibition of GCs. This circuit reorganization provides a mechanism by which mature GCs could escape the strong inhibition they receive, creating a window of opportunity for plasticity. Indeed, coincident activation of perforant path inputs with optogenetic release of acetylcholine produced a long-term potentiated response in GCs, essential for memory formation.

neuroscience↗