Mayer, M. I. | bioRxiv Science

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↗