Biology subjects

Nyiri, G.

Publications and source records attributed to Nyiri, G..

5 recordsLinked to original sources

bioRxiv2026

Hippocampo-septal inhibitory feedback controls the medial septal circuit as a function of brain state, pyramidal cell activity and movement speed.

Encoding novel experiences and retrieving stored information rely on the hippocampal theta rhythm in several mammalian species. Coordination of putative pacemakers in the medial septum (MS) by the GABAergic hippocampo-septal (HS) feedback is hypothesized to be essential for theta genesis. In order to reveal how the HS-feedback controls the MS circuit, and through it hippocampal oscillations in general, we set out to uncover the behavior-related activity of HS neurons as well as how different components of the MS network are regulated by the HS-feedback. Utilizing computational modelling and in vivo optogenetic manipulation of the HS pathway, we show that the HS feedback is not required for theta generation, which is primarily governed by intra-MS connections. HS blockade did not alter the phase coupling of MS neurons to hippocampal theta rhythm nor the synchrony between rhythmic MS neurons but augmented ongoing theta and coupled mid-gamma oscillations in the hippocampus. By contrast, correlated activity between non-rhythmic MS neurons was sensitive to HS blockade. Moreover, the HS feedback scaled with hippocampal activity and running speed. In turn, modulation of MS neurons by running and ripples was diminished by the transient suppression of HS terminals. These findings suggest that the HS feedback exerts inhibitory control of the MS depending upon hippocampal output and movement speed.

neuroscience↗

bioRxiv2023

Absolute number of three populations of interneurons and GABAergic synapses in the human hippocampus

The human hippocampus, essential for learning and memory, is implicated in numerous neurological and psychiatric disorders, each linked to specific neuronal subpopulations. Advancing our understanding of hippocampal function requires computational models grounded in precise quantitative neuronal data. While extensive data exist on the neuronal composition and synaptic architecture of the rodent hippocampus, analogous quantitative data for the human hippocampus remain very limited. Given the critical role of local GABAergic interneurons in modulating hippocampal functions, we employed unbiased stereological techniques to estimate the density and total number of three major GABAergic cell types in the human hippocampus: parvalbumin (PV)-expressing, somatostatin (SOM)-positive, and calretinin (CR)-positive interneurons. Our findings reveal an estimated 49,400 PV-positive, 141,500 SOM-positive, and 250,600 CR-positive interneurons per hippocampal hemisphere. Notably, the higher proportion of CR-positive, primarily interneuron-selective, cells in humans, compared to rodents, may enhance local interneuron regulation. Additionally, using 3-dimensional electron microscopy, we estimated approximately 25 billion GABAergic synapses per hippocampal hemisphere, with PV-positive boutons comprising around 3.5 billion synapses, or 14% of the total GABAergic synapses. These findings contribute crucial quantitative insights for modeling human hippocampal circuits and understanding its complex regulatory dynamics.

neuroscience↗

bioRxiv2023

Synaptic and dendritic architecture of two types of hippocampal somatostatin interneurons

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed and make available several key datasets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The dataset includes detailed scanning electron microscopy-based 3-dimensional reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core dataset with other anatomical data, patch-clamp electrophysiology and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For instance, we estimated that an OLM cell receives about 8400, whereas an HS cell about 15600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.

neuroscience↗

bioRxiv2023

Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system. While they have a well-documented role in the regulation of sleep-wake states, whether and how BFPVNs participate in mediating awake behaviors is not known. To address this, we performed bulk calcium imaging and recorded single neuronal activity from the horizontal band of the diagonal band of Broca (HDB) while mice were performing an associative learning task. Genetically identified BFPVNs of the HDB responded with a distinctive, phasic activation to punishment. In contrast, reward only elicited slow and delayed responses, while stimuli predicting behavioral reinforcement (reward or punishment) were followed by a gradual increase of HDB BFPVN firing rates. Optogenetic inhibition of HDB BFPVNs during punishment impaired the formation of cue-outcome associations, suggesting a causal role of these neurons in associative learning. Mapping the input-output connectivity of HDB BFPVNs by anterograde and mono-transsynaptic retrograde tracing experiments showed that these neurons received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key structures of the limbic system including the medial septum, the retrosplenial cortex and the hippocampus. Bulk calcium imaging performed in these termination regions indicated that HDB BFPVNs broadcast information about aversive stimuli to multiple downstream targets. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions during awake behaviors.

neuroscience↗

bioRxiv2017

Synaptic co-transmission of acetylcholine and GABA regulates hippocampal states

The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter, acetylcholine. Yet, using immune-electron tomographic, molecular anatomical, optogenetic and physiological techniques, we find that mouse hippocampal cholinergic terminals invariably establish synapses and their vesicles dock at synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes fast composite postsynaptic potentials, which are mutually cross-regulated by presynaptic auto-receptors and display different short-term plasticity. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. The synaptic nature of the forebrain cholinergic system with differentially regulated, fast, GABAergic and cholinergic co-transmission suggests a hitherto unrecognized level of synaptic control over cortical states. This novel model of hippocampal cholinergic neurotransmission could form the basis for alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders.\n\nSupplementary materials are attached after the main text.

neuroscience↗