1.GABAergic interneuronal loss and reduced inhibitory synaptic transmission in the hippocampal CA1 region after mild traumatic brain injury.
Almeida-Suhett CP1, Prager EM2, Pidoplichko V3, Figueiredo TH4, Marini AM5, Li Z6, Eiden LE7, Braga MF8. Exp Neurol. 2015 Nov;273:11-23. doi: 10.1016/j.expneurol.2015.07.028. Epub 2015 Jul 31.
Patients that suffer mild traumatic brain injuries (mTBI) often develop cognitive impairments, including memory and learning deficits. The hippocampus shows a high susceptibility to mTBI-induced damage due to its anatomical localization and has been implicated in cognitive and neurological impairments after mTBI. However, it remains unknown whether mTBI cognitive impairments are a result of morphological and pathophysiological alterations occurring in the CA1 hippocampal region. We investigated whether mTBI induces morphological and pathophysiological alterations in the CA1 using the controlled cortical impact (CCI) model. Seven days after CCI, animals subjected to mTBI showed cognitive impairment in the passive avoidance test and deficits to long-term potentiation (LTP) of synaptic transmission. Deficiencies in inducing or maintaining LTP were likely due to an observed reduction in the activation of NMDA but not AMPA receptors. Significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs) were also observed 7 days after CCI.
2.TRH modulates glutamatergic synaptic inputs on CA1 neurons of the mouse hippocampus in a biphasic manner.
Zarif H1, Petit-Paitel A1, Heurteaux C1, Chabry J1, Guyon A2. Neuropharmacology. 2016 Apr 6. pii: S0028-3908(16)30140-X. doi: 10.1016/j.neuropharm.2016.04.004. [Epub ahead of print]
Thyrotropin releasing hormone (TRH) is a tripeptide that induces the release of Thyroid Stimulating Hormone (TSH) in the blood. Besides its role in the thyroid system, TRH has been shown to regulate several neuronal systems in the brain however its role in hippocampus remains controversial. Using electrophysiological recordings in acute mouse brain slices, we show that TRH depresses glutamate responses at the CA3-CA1 synapse through an action on NMDA receptors, which, as a consequence, decreases the ability of the synapse to establish a long term potentiation (LTP). TRH also induces a late increase in AMPA/kainate responses. Together, these results suggest that TRH plays an important role in the modulation of hippocampal neuronal activities, and they contribute to a better understanding of the mechanisms by which TRH impacts synaptic function underlying emotional states, learning and memory processes.
3.Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.
Stern S1, Agudelo-Toro A2, Rotem A3, Moses E1, Neef A2. PLoS One. 2015 Jul 17;10(7):e0132577. doi: 10.1371/journal.pone.0132577. eCollection 2015.
Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD) curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms.
4.CNQX facilitates inhibitory synaptic transmission in rat hypoglossal nucleus.
Han L1, Mu S1, He Z1, Wang Z2, Qu J3, Ye W4, Zhang J5. Brain Res. 2016 Apr 15;1637:71-80. doi: 10.1016/j.brainres.2016.02.020. Epub 2016 Feb 18.
6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) is a most commonly used antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in the central nervous system. During the past two decades, studies had demonstrated that CNQX could partially activate AMPA receptors that are located on the hippocampal and cerebellar interneurons, thus subsequently leading to the facilitation of inhibitory transmission. However, whether CNQX could enhance inhibitory synaptic transmission in the hypoglossal nucleus remains elusive. Here, using whole-cell patch-clamp recording in the brainstem slice, we showed that CNQX greatly increased both frequency and amplitude of spontaneous inhibitory postsynaptic currents in the hypoglossal motoneurons, whereas D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), N-methyl-D-aspartate (NMDA) receptor antagonist, had no effect on inhibitory synaptic transmission. Application of bicuculline and strychnine further identified that CNQX not only increased GABAergic sIPSCs but also glycinergic one in these motoneurons.