Biology subjects

Hochner, B.

Publications and source records attributed to Hochner, B..

6 recordsLinked to original sources

bioRxiv2025

Cellular and synaptic organization of the Octopus vertical lobe

Understanding memory formation and its influence on behavior is a central challenge in neuroscience. Associative learning networks, including the mushroom body in insects, the cerebellum in mammals, and the vertical lobe (VL) in cephalopods, typically exhibit a 3-layered architecture, characterized by divergence (fan-out) followed by convergence (fan-in), facilitating sparse sensory coding (Babadi and Sompolinsky, 2014; Lin et al., 2014; Litwin-Kumar et al., 2017; Turchetti-Maia et al., 2017). Previously, using volumetric electron microscopy, we showed that the VL uniquely comprises 22 million simple amacrine (SAM) interneurons, each receiving a singular input subject to activity-dependent long-term potentiation, contrasting with typical middle-layer interneurons (Bidel, Meirovitch et al., 2023). We also demonstrated that these SAMs provide excitatory feedforward input to the output cell layer, balanced by approximately 400,000 inhibitory complex amacrines (CAM), which are morphologically diverse and integrate numerous inputs (Bidel, Meirovitch et al., 2023). Here, we leverage the same digital tissue to explore the CAMs morphological diversity, identifying correlations between structure, postsynaptic site density, and synaptic input proportions, which led to the classification of CAMs into distinct groups. Further analysis of the input layer in the VL revealed a meticulous structural and synaptic compartmentalization, with distinct synaptic bouton types forming three zones that integrate different inputs towards CAMs. Additionally, we identify the potential presence of a neurogenic niche in the VL, hinting at parallels with neurogenic processes in other species and warranting further investigation, particularly in the context of learning and memory. This study deepens our understanding of the VLs cellular and synaptic architecture, revealing both shared and unique features compared to other associative networks, and highlighting the intricate interplay of structural and functional elements in memory formation. Highlights (85 characters including space)O_LIThe VL both aligns with and deviates from standard associative network features C_LIO_LIThe VL input layer presents a unique compartmentalization by axonal bouton type C_LIO_LIThe minority inhibitory interneurons differentiate into unique functional subtypes C_LIO_LIMirroring the mammalian hippocampus, the VL may contain an adult neurogenic niche C_LI

neuroscience↗

bioRxiv2024

A novel nitric oxide (NO)-dependent 'molecular switch' mediates LTP in the Octopus vulgaris brain through persistent activation of nitric oxide synthase (NOS)

Cephalopods are a renowned example of the independent evolution of complex behavior in invertebrates. The octopuss outstanding learning capability is a prominent feature that depends on the vertical lobe (VL). Previously, we found that the synaptic input into the VL exhibits robust activity-dependent long-term potentiation (LTP) mediated by molecular processes that are only partially understood. Here, we reveal that the VL LTP is mediated by nitric oxide (NO). In contrast to the prevailing dogma, in the octopus VL, NO does not mediate LTP induction, as tetanization-induced LTP occurs even in the presence of NO-synthase (NOS) inhibitors. Remarkably, however, NOS inhibitors block the long-term presynaptic expression of LTP, and high doses of NO donor induce short-term synaptic potentiation, suggesting that a persistent elevation of NO concentration mediates LTP expression. Moreover, in a distinct group of synapses, NOS inhibitors also disrupted LTP maintenance, as following drug washout, a high-frequency stimulation reinstated full LTP, suggesting that NO is also involved in maintaining LTP. We propose a novel molecular-switch mechanism whereby a positive feedback loop of NO-dependent NOS reactivation mediates persistent NOS activation, thus providing an LTP maintenance mechanism. Subsequently, retrograde NO diffusion facilitates presynaptic transmitter release, driving LTP expression. These findings demonstrate how evolutionary adaptation of molluscan molecular mechanisms has contributed to the emergence of the advanced cognitive abilities observed in octopuses.

neuroscience↗

bioRxiv2023

mEMbrain: an interactive deep learning MATLAB tool for connectomic segmentation on commodity desktops

Connectomics is fundamental in propelling our understanding of the nervous systems organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from 4 different animals and 5 datasets, amounting to around 180 hours of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of 4 pre-trained networks for said datasets. All tools are available from https://lichtman.rc.fas.harvard.edu/mEMbrain/. With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.

neuroscience↗

bioRxiv2022

Connectomics of the Octopus vulgaris vertical lobe provides insight into conserved and novel principles of a memory acquisition network

We present the first analysis of the connectome of the vertical lobe (VL) of Octopus vulgaris, a brain structure mediating acquisition of long-term memory in this behaviorally advanced mollusk. Serial section electron microscopy revealed new types of interneurons, cellular components of extensive modulatory systems and multiple synaptic motifs. The sensory input to the VL is conveyed via ~1,800,000 axons that sparsely innervate two parallel and interconnected feedforward networks formed by the two types of amacrine interneurons (AM), simple AMs (SAMs) and complex AMs (CAMs). SAMs make up 89.3% of the ~25,000,000 VL cells, each receiving a synaptic input from only a single input neuron on its non-bifurcating primary neurite, suggesting that each input neuron is represented in only ~12 SAMs. This synaptic site is likely a "memory site" as it is endowed with LTP. The CAMs, a newly described AM type, comprise 1.6% of the VL cells. Their bifurcating neurites integrate multiple inputs from the input axons and SAMs. While the SAM network appears to feedforward sparse "memorizable" sensory representations into the VL output layer, the CAMs appear to monitor global activity and feedforward a balancing inhibition for "sharpening" the stimulus-specific VL output. While sharing morphological and wiring features with circuits supporting associative learning in other animals, the VL has evolved a unique circuit that enables associative learning based strictly on feedforward information flow.

neuroscience↗

bioRxiv2021

Neurotransmission and neuromodulation systems in the learning and memory network of Octopus vulgaris

The vertical lobe (VL) in the octopus brain plays an essential role in its sophisticated learning and memory. Early anatomical studies suggested that the VL is organized in a "fan-out fan-in" connectivity matrix comprising only three morphologically identified neuron types; input axons from the superior frontal lobe (SFL) innervating en passant millions of small amacrine interneurons (AMs) which converge sharply onto large VL output neurons (LNs). Recent physiological studies confirmed the feedforward excitatory connectivity: a glutamatergic synapse at the first SFL-to-AM synaptic layer and a cholinergic AM-to-LNs synapse. SFL-to-AMs synapses show a robust hippocampal-like activity-dependent long-term potentiation (LTP) of transmitter release. 5-HT, octopamine, dopamine and nitric oxide modulate short- and long-term VL synaptic plasticity. Here we present a comprehensive histolabeling study to better characterize the neural elements in the VL. We generally confirmed glutamatergic SFLs and cholinergic AMs. Intense labeling for NOS activity in the AMs neurites fitted with the NO-dependent presynaptic LTP mechanism at the SFL-to-AM synapse. New discoveries here reveal more heterogeneity of the VL neurons than previously thought. GABAergic AMs suggest a subpopulation of inhibitory interneurons in the first input layer. Clear GABA labeling in the cell bodies of LNs supported an inhibitory VL output yet the LNs co-expressed FMRFamide-like neuropeptides suggesting an additional neuromodulatory role of the VL output. Furthermore, a group of LNs was glutamatergic. A new cluster of cells organized in a "deep nucleus" showed rich catecholaminergic labeling and may play a role in intrinsic neuromodulation. In situ hybridization and immunolabeling allowed characterization and localization of a rich array of neuropeptides and neuromodulatores, likely involved in reward/punishment signals. This analysis of the fast transmission system, together with the newly found cellular elements helps integrate behavioral, physiological, pharmacological and connectome findings into a more comprehensive understanding of an efficient learning and memory network.

neuroscience↗

bioRxiv2018

A novel NO-dependent \"molecular-memory-switch\" mediates presynaptic expression and postsynaptic maintenance of LTP in the octopus brain

The octopus brain shows a robust hippocampal-like activity-dependent LTP, which is NMDA-independent, yet associative and presynaptically expressed and, as shown here, also independent of protein synthesis. Have the molecular mechanisms for mediating this LTP evolved independently or have they converged? Here we report on a distinctive adaptation of the nitric-oxide (NO) system for mediation of the octopus LTP. Unlike the suggested role of NO in LTP induction in the hippocampus, in octopus, inhibitors of NO-synthase (NOS) did not block LTP induction but either 1) reversibly erased LTP expression, suggesting that a constitutive elevation in NO mediates the presynaptic LTP expression or 2) reversed LTP induction and maintenance because a second LTP could be induced after inhibitor washout. We therefore propose a protein synthesis-independent molecular-switch, whereby NO-dependent NOS reactivation maintains NOS in its active state. Thus, while the octopus LTP shows marked evolutionary convergence with LTP in vertebrates, an extreme molecular novelty has evolved to mediate it.

neuroscience↗