Biology subjects

Furdan, S.

Publications and source records attributed to Furdan, S..

3 recordsLinked to original sources

bioRxiv2021

Somatic HCN channels augment and speed up GABAergic basket cell input-output function in human neocortex

Neurons in the mammalian brain exhibit evolution-driven species-specific differences in their functional properties. Therefore, understanding the human brain requires unraveling the human neuron "uniqueness" and how it contributes to the operation of specific neuronal circuits. We show here that a highly abundant type of inhibitory neurons in the neocortex, GABAergic parvalbumin-expressing basket cell (pv+BC), exhibits in the human brain a specific somatic leak current mechanism, which is absent in their rodent neuronal counterparts. Human pv+BC soma shows electric leak conductance mediated by hyperpolarization-activated cyclic nucleotide-gated channels. This leak conductance has depolarizing effects on the resting membrane potential and it accelerates the rise of synaptic potentials in the cell soma. The leak facilitates the human pv+BC input-to-output fidelity and shortens the action potential generation to excitatory inputs. This mechanism constitutes an adaptation that enhances signal transmission fidelity and speed in the common inhibitory circuit in the human but not in the rodent neocortex.

neuroscience↗

bioRxiv2020

Disinhibition mediated by reciprocal hypothalamic and raphe GABAergic projections promotes wakefulness

The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as the dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these systems are just beginning to be explored. Using a combination of viral tracing, circuit mapping, electrophysiological recordings from identified neurons and combinatorial optogenetics in mice, we show that GABAergic neurons in the LH selectively inhibit GABAergic neurons in the DR resulting in increased firing of a substantial fraction of its neurons that ultimately promotes arousal. These DRGABA neurons are wake active and project to multiple brain areas involved in the control of arousal including the LH, where their specific activation potently influences local network activity leading to arousal from sleep. Our results show how mutual inhibitory projections between the LH and the DR promote wakefulness and suggest a complex arousal control by intimate interactions between long-range connections and local circuit dynamics.

neuroscience↗

bioRxiv2020

Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

The neocortex is disproportionately expanded in human compared to mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers that selectively make connections within the cortex and other telencephalic structures. Single-cell transcriptomic analyses of human and mouse cortex show an increased diversity of glutamatergic neuron types in supragranular cortex in human and pronounced gradients as a function of cortical depth. To probe the functional and anatomical correlates of this transcriptomic diversity, we describe a robust Patch-seq platform using neurosurgically-resected human tissues. We characterize the morphological and physiological properties of five transcriptomically defined human glutamatergic supragranular neuron types. Three of these types have properties that are specialized compared to the more homogeneous properties of transcriptomically defined homologous mouse neuron types. The two remaining supragranular neuron types, located exclusively in deep layer 3, do not have clear mouse homologues in supragranular cortex but are transcriptionally most similar to deep layer mouse intratelencephalic-projecting neuron types. Furthermore, we reveal the transcriptomic types in deep layer 3 that express high levels of non-phosphorylated heavy chain neurofilament protein that label long-range neurons known to be selectively depleted in Alzheimers disease. Together, these results demonstrate the power of transcriptomic cell type classification, provide a mechanistic underpinning for increased complexity of cortical function in human cortical evolution, and implicate discrete transcriptomic cell types as selectively vulnerable in disease.

neuroscience↗