Brickley, S. G. | bioRxiv Science

bioRxiv2024

The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons.

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neurons selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

neuroscience↗

bioRxiv2022

Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

We studied how co-release of histamine/GABA from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influences circuit processing. We opto-stimulated histamine/GABA co-release from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings were used to monitor excitability of visually identified PFC neurons in layer 2/3 of prelimbic (PL), anterior cingulate (AC) and infralimbic (IL) regions before and after opto-stimulated histamine/GABA release. We found that histamine-GABA co-release influences the PFC through actions on distinct neuronal types: histamine stimulates fast-spiking interneurons; and co-released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast spiking non-accommodating interneurons, opto-stimulation increased excitability, an effect blocked by histamine H1 and H2 receptor antagonists. The excitability of other interneuron types in the PFC was not altered. In contrast, the combined action of histamine and GABA co-release from TMNHDC axons produced predominantly divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. The direct inhibitory effect of TMNHDC axon activation on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult lifespan (from 3 months to over 2 years of age), stimulation of TMNHDC axons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals that maintain cognitive performance into later life, increases in TMNHDC modulation of PyrNs could enhance information processing and be an adaptive mechanism to buttress cognition.

neuroscience↗