Long-term potentiation of glycinergic synapses by semi-natural stimulation patterns during tonotopic map refinement

Before the onset of hearing, cochlea-generated patterns of spontaneous spike activity drive the maturation of central auditory circuits. In the glycinergic sound localization pathway from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO) this spontaneous activity guides the strengthening and silencing of synapses which underlies tonotopic map refinement. However, the mechanisms by which patterned activity regulates synaptic refinement in the MNTB-LSO pathway are still poorly understood. To address this question, we recorded from LSO neurons in slices from prehearing mice while stimulating MNTB afferents with stimulation patterns that mimicked those present in vivo. We found that these semi-natural stimulation patterns reliably elicited a novel form of long-term potentiation (LTP) of MNTB-LSO synapses. Stimulation patterns that lacked the characteristic high-frequency (200 Hz) component of prehearing spike activity failed to elicit potentiation. LTP was calcium dependent, required the activation of both g-protein coupled GABAB and metabotropic glutamate receptors and involved an increase in postsynaptic glycine receptor-mediated currents. Our results provide a possible mechanism linking spontaneous spike bursts to tonotopic map refinement and further highlight the importance of the co-release of GABA and glutamate from immature glycinergic MNTB terminals.

Proprioceptive and cutaneous sensations in humans elicited by intracortical microstimulation

Pioneering work with nonhuman primates and recent human studies established intracortical microstimulation (ICMS) in primary somatosensory cortex (S1) as a method of inducing discriminable artificial sensation. However, these artificial sensations do not yet provide the breadth of cutaneous and proprioceptive percepts available through natural stimulation. In a tetraplegic human with two microelectrode arrays implanted in S1, we report replicable elicitations of sensations in both the cutaneous and proprioceptive modalities localized to the contralateral arm, dependent on both amplitude and frequency of stimulation. Furthermore, we found a subset of electrodes that exhibited multimodal properties, and that proprioceptive percepts on these electrodes were associated with higher amplitudes, irrespective of the frequency. These novel results demonstrate the ability to provide naturalistic percepts through ICMS that can more closely mimic the body’s natural physiological capabilities. Furthermore, delivering both cutaneous and proprioceptive sensations through artificial somatosensory feedback could improve performance and embodiment in brain-machine interfaces.

Tissue adaptation: Implications for gut immunity and tolerance

Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.

Tissue adaptation: implications for gut immunity and tolerance

Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.