Biology subjects

Hajos, N.

Publications and source records attributed to Hajos, N..

9 recordsLinked to original sources

bioRxiv2026

The Amygdalostriatal Transition Area Exhibits Lateral Amygdala-Like Spiking Activity and Tone-Shock Pairing-Induced Plasticity

During Pavlovian fear conditioning, presentation of a conditioned stimulus, such as a tone, together with an unconditioned stimulus, such as an electrical shock, excites neurons in the lateral amygdala (LA). Prevailing models propose that sensory stimulus-evoked activity in the LA is subsequently propagated to its downstream nuclei: the basal amygdala (BA) and central amygdala (CeA). To test this assumption, we performed in vivo electrophysiological recordings in awake, head-fixed male and female mice. We found that tone presentation did not elicit a significant increase in firing in BA or CeA neurons. In contrast, shock presentation evoked similarly robust spiking responses in LA and BA neurons but only a modest increase in CeA neurons. Notably, neurons in the amygdalostriatal transition area (AStria) exhibited LA-like sensory stimulus-evoked responses at both short (<25 ms) and longer (<500 ms) timescales. To examine the role of feedforward inhibition in tone- and shock-evoked activity, we investigated the contribution of parvalbumin interneurons using optogenetics and found that short-latency (<25 ms) spiking in both the LA and AStria was regulated by these inhibitory cells. Finally, LA and AStria neurons exhibited remarkably similar response types, spiking dynamics, and pairing-induced plasticity during repeated tone presentations, subsequent tone-shock pairings, and post-pairing tone presentations. Together, these findings support a model in which the LA and AStria operate in parallel, similarly integrating tone and shock signals during fear conditioning, whereas BA and CeA neurons are not robustly recruited by these sensory stimuli under the conditions tested.

neuroscience↗

bioRxiv2026

Sensory stimulation triggers different spike responses in serotonin and dopamine neurons in the dorsal midbrain tegmentum.

The dorsal midbrain tegmentum, including the dorsal raphe nucleus (DRN) and the ventrolateral periaqueductal gray (vlPAG), contains diverse neuronal populations. Within this region, serotonin (5-HT) and dopamine (DA) neurons are the principal monoaminergic cell types and exert widespread influence on brain circuits. While the role of 5-HT and DA neurons in sensory integration is well established, their stimulus-driven spiking activity remains incompletely characterized. Using silicon probe recordings in mice, we found that >57% of DRN/vlPAG neurons responded to foot shock and mechanical stimulation, whereas <15% showed changes in spiking activity following light or acoustic stimulation. At the population level, similar results were obtained using juxtacellular recordings, a method that allowed post hoc identification of 5-HT and DA neurons. Upon foot shock delivery, 5-HT neurons exhibited heterogeneous responses, including both excitation and inhibition, whereas DA neurons typically increased their firing rates. We found that DA neurons lacking vasoactive intestinal polypeptide (VIP) fired within the first second after foot shocks, while VIP-expressing DA neurons were most active later. Together, our results demonstrate that DRN/vlPAG neurons are most responsive to foot shock and mechanical stimuli. Moreover, 5-HT and DA neurons exhibit distinct patterns of activation following aversive inputs, suggesting that they play different roles in sensory information processing.

neuroscience↗

bioRxiv2024

Synaptic communication within the microcircuits of pyramidal neurons and basket cells in the mouse prefrontal cortex

Basket cells are inhibitory interneurons in cortical structures with the potential to efficiently control the activity of their postsynaptic partners. Although their contribution to higher order cognitive functions associated with the medial prefrontal cortex (mPFC) relies on the characteristics of their synaptic connections, the way they are embedded into local circuits is still not fully uncovered. Here, we determined the synaptic properties of excitatory and inhibitory connections between pyramidal neurons (PNs), cholecystokinin-containing basket cells (CCKBCs) and parvalbumin-containing basket cells (PVBCs) in the mouse mPFC. By performing paired recordings, we revealed that PVBCs receive larger unitary excitatory postsynaptic currents from PNs with shorter latency and faster kinetic properties compared to events evoked in CCKBCs. Also, unitary inhibitory postsynaptic currents in PNs were more reliably evoked by PVBCs than by CCKBCs yet the former connections showed profound short-term depression. Moreover, we demonstrated that CCKBCs and PVBCs in the mPFC are mutually interconnected with each other. As alterations in PVBC function have been linked to neurological and psychiatric conditions like Alzheimers disease and schizophrenia and CCKBC vulnerability might play a role in mood disorders, a deeper understanding of the general features of basket cell synapses could serve as a reference point for future investigations with therapeutic objectives.

neuroscience↗

bioRxiv2023

Diversity and connectivity of principal neurons in the lateral and basal nuclei of the mouse amygdala

The basolateral amygdala is a non-layered cortical structure playing a role in various cognitive processes. Despite many studies focusing on local information processing within the circuits of the basolateral amygdala, the characteristics of excitatory principal neurons (PNs) are still not fully revealed. Here, we combined neuroanatomical, electrophysiological, and tracing techniques to determine the single-cell features, dendritic and axonal projections of PNs within the lateral (LA) and basal amygdala (BA). Using a mouse reporter line, we found that cholecystokinin (CCK) expression defines two spatially and functionally segregated groups of PNs both in the LA and BA. PNs in CCK-positive (CCK+) areas of the LA (LAa) had small somata and short dendrites which matched their single-cell electrophysiological properties. PNs in CCK-negative (CCK-) areas of the LA (LAp) and all BA had similarly ramified dendrites and single-cell features with some differences. Importantly, the dendritic arbors of PNs were restricted to the subnuclei defined by CCK expression, which corresponded to various extra-amygdalar afferents indicating specific inputs on distinct PN groups. Axonal arborization patterns of PNs within the basolateral amygdala and surrounding areas showed consistency to their soma location. For instance, BA PNs that projected to the medial prefrontal cortex but not to the lateral nucleus of the central amygdala were present in CCK+ areas. In contrast, those BA PNs that projected to the lateral part of the central nucleus were found in the subnucleus lacking CCK. Our study revealed that the basolateral amygdala is composed of functionally different subnuclei with specific inputs and outputs. This structural arrangement may empower the LA and BA to flexibly channel processed information toward their downstream regions, which can be a key requirement for diverse amygdala functions in cognitive operation.

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bioRxiv2023

Functionally linked amygdala and prefrontal cortical regions are innervated by both single and double projecting cholinergic neurons

Cholinergic cells have been proposed to innervate simultaneously those cortical areas that are mutually interconnected with each other. To test this hypothesis, we investigated the cholinergic innervation of functionally linked amygdala and prefrontal cortical regions. First, using tracing experiments, we determined that cholinergic cells located in distinct basal forebrain (BF) areas projected to the different nuclei of the basolateral amygdala (BLA). Specifically, cholinergic cells in the ventral pallidum/substantia innominata (VP/SI) innervated the basal nucleus (BA), while the horizontal limb of the diagonal band of Broca (HDB) projected to its basomedial nucleus (BMA). In addition, cholinergic neurons in these two BF areas gave rise to overlapping innervation in the medial prefrontal cortex (mPFC), yet their axons segregated in the dorsal and ventral regions of the PFC. Using retrograde-anterograde viral tracing, we demonstrated that a portion of mPFC-projecting cholinergic neurons also innervated the BLA, especially the BA. By injecting retrograde tracers into the mPFC and BA, we found that 28% of retrogradely labeled cholinergic cells were double labeled, which typically located in the VP/SI. In addition, we found that vesicular glutamate transporter type 3 (VGLUT3)-expressing neurons within the VP/SI were also cholinergic and projected to the mPFC and BA, implicating that a part of the cholinergic afferents may release glutamate. In contrast, we uncovered that GABA is unlikely to be a co-transmitter molecule in HDB and VP/SI cholinergic neurons in adult mice. The dual innervation strategy, i.e., the existence of cholinergic cell populations with single as well as simultaneous projections to the BLA and mPFC, provides the possibility for both synchronous and independent control of the operation in these cortical areas, a structural arrangement that may maximize computational support for functionally linked regions. The presence of VGLUT3 in a portion of cholinergic afferents suggests more complex functional effects of cholinergic system in cortical structures.

neuroscience↗

bioRxiv2023

Structural organisation of perisomatic inhibition in the mouse medial prefrontal cortex

Perisomatic inhibition profoundly controls neural function. However, the structural organisation of inhibitory circuits giving rise to the perisomatic inhibition in the higher-order cortices is not completely known. Here, we performed a comprehensive analysis of those GABAergic cells in the medial prefrontal cortex (mPFC) that provide inputs onto the somata and proximal dendrites of pyramidal neurons. Our results show that most GABAergic axonal varicosities contacting the perisomatic region of superficial (layer 2/3) and deep (layer 5) pyramidal cells express parvalbumin (PV) or cannabinoid receptor type 1 (CB1). Further, we found that the ratio of PV/CB1 GABAergic inputs is larger on the somatic membrane surface of pyramidal tract neurons in comparison to those projecting to the contralateral hemisphere. Our morphological analysis of in vitro labelled PV+ basket cells (PVBC) and CCK/CB1+ basket cells (CCKBC) revealed differences in many features. PVBC dendrites and axons arborized preferentially within the layer where their soma was located. In contrast, the axons of CCKBCs expanded throughout layers, though their dendrites were found preferentially either in superficial or deep layers. Finally, using anterograde trans-synaptic tracing we observed that PVBCs are preferentially innervated by thalamic and basal amygdala afferents in layer 5a and 5b, respectively. Thus, our results suggest that PVBCs can control the local circuit operation in a layer-specific manner via their characteristic arborization, while CCKBCs rather provide cross-layer inhibition in the mPFC. Significance StatementInhibitory cells in cortical circuits are crucial for the precise control of local network activity. Nevertheless, in higher-order cortical areas that are involved in cognitive functions like decision making, working memory and cognitive flexibility, the structural organisation of inhibitory cell circuits is not completely understood. In this study we show that perisomatic inhibitory control of excitatory cells in the medial prefrontal cortex is performed by two types of basket cells endowed with different morphological properties that provide inhibitory inputs with distinct layer specificity on cells projecting to disparate areas. Revealing this difference in innervation strategy of the two basket cell types is a key step towards understanding how they fulfil their distinct roles in cortical network operations.

neuroscience↗

bioRxiv2022

CaMKIIα promoter-controlled circuit manipulations target both pyramidal cells and inhibitory interneurons in cortical networks

A key assumption in studies of cortical functions is that excitatory principal neurons, but not inhibitory cells express calcium/calmodulin-dependent protein kinase II subunit (CaMKII) resulting in a widespread use of CaMKII promoter-driven protein expression for principal cell manipulation and monitoring their activities. Using neuroanatomical and electrophysiological methods we demonstrate that in addition to pyramidal neurons, multiple types of cortical GABAegic cells are targeted by adeno-associated viral vector (AAV) carrying the CaMKII-Channelrhodopsin 2-mCherry construct. We show that the reporter protein, mCherry can visualize a large fraction of different interneuron types, including parvalbumin (PV), somatostatin (SST), neuronal nitric oxide synthase (nNOS) and neuropeptide Y (NPY)-containing GABAergic cells, which altogether cover around 50% of the whole inhibitory cell population in cortical structures. Importantly, the expression of the excitatory opsin Channelrhodopsin 2 in the interneurons effectively drive spiking of infected GABAergic cells even if the detectability of reporter proteins is ambiguous. Thus, our results challenge the use of CaMKII promoter-driven protein expression as a selective tool in targeting cortical glutamatergic neurons using viral vectors.

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bioRxiv2021

Total number and ratio of GABAergic neuron types in the mouse lateral and basal amygdala

GABAergic neurons are key circuit elements in cortical networks. In spite of growing evidence showing that inhibitory cells play a critical role in the lateral (LA) and basal (BA) amygdala functions, neither the number of GABAergic neurons nor the ratio of their distinct types have been determined in these amygdalar nuclei. Using unbiased stereology, we found that the ratio of GABAergic neurons in the BA (22 %) is significantly higher than in the LA (16 %) in both male and female mice. No difference was observed between the right and left hemispheres in either sexes. In addition, we assessed the ratio of the major inhibitory cell types in both amygdalar nuclei. Using transgenic mice and a viral strategy for visualizing inhibitory cells combined with immunocytochemistry, we estimated that the following cell types together compose the vast majority of GABAergic cells in the LA and BA: axo-axonic cells (5.5-6 %), basket cells expressing parvalbumin (17-20 %) or cholecystokinin (7-9 %), dendrite-targeting inhibitory cells expressing somatostatin (10-16 %), NPY-containing neurogliaform cells (14-15 %), VIP and/or calretinin-expressing interneuron-selective interneurons (29-38 %) and GABAergic projection neurons expressing somatostatin and neuronal nitric oxide synthase (nNOS, 5.5-8 %). Our results show that these amygdalar nuclei contain all major GABAergic neuron types as found in other cortical regions. Furthermore, our data offer an essential reference for future studies aiming to reveal changes in GABAergic cell number and in inhibitory cell types typically observed under different pathological conditions, and to model functioning amygdalar networks in health and disease. Significance statementGABAergic cells in cortical structures, like in the lateral and basal nucleus of the amygdala, have a determinant role in controlling circuit operation. In this study, we provide the first estimate for the total number of inhibitory cells in these two amygdalar nuclei. In addition, our study is the first to define the ratio of the major GABAergic cell types present in these cortical networks. Taking into account that hyper-excitability in the amygdala, arising from the imbalance between excitation and inhibition typifies many altered brain functions including anxiety, posttraumatic stress disorder, schizophrenia and autism, uncovering the number and ratio of distinct amygdalar inhibitory cell types offers a solid base for comparing the changes in inhibition in pathological brain states.

neuroscience↗

bioRxiv2021

Hippocampal sharp wave-ripples and the associatedsequence replay emerge from structured synapticinteractions in a network model of area CA3

Hippocampal place cells are activated sequentially as an animal explores its environment. These activity sequences are internally recreated ("replayed"), either in the same or reversed order, during bursts of activity (sharp wave-ripples; SWRs) that occur in sleep and awake rest. SWR-associated replay is thought to be critical for the creation and maintenance of long-term memory. In order to identify the cellular and network mechanisms of SWRs and replay, we constructed and simulated a data-driven model of area CA3 of the hippocampus. Our results show that the chain-like structure of recurrent excitatory interactions established during learning not only determines the content of replay, but is essential for the generation of the SWRs as well. We find that bidirectional replay requires the interplay of the experimentally confirmed, temporally symmetric plasticity rule, and cellular adaptation. Our model provides a unifying framework for diverse phenomena involving hippocampal plasticity, representations, and dynamics, and suggests that the structured neural codes induced by learning may have greater influence over cortical network states than previously appreciated.

neuroscience↗