Front Neural Circuit
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Front Neural Circuit · Jan 2013
Changes in the expression of GABAA receptor subunit mRNAs in parahippocampal areas after kainic acid induced seizures.
The parahippocampal areas including the subiculum, pre- and parasubiculum, and notably the entorhinal cortex (EC) are intimately involved in the generation of limbic seizures in temporal lobe epilepsy. We investigated changes in the expression of 10 major GABAA receptor subunit mRNAs in subfields of the ventral hippocampus, ventral subiculum, EC, and perirhinal cortex (PRC) at different intervals (1, 8, 30, and 90 days) after kainic acid (KA)-induced status epilepticus priming epileptogenesis in the rat. The most pronounced and ubiquitous changes were a transient (24 h after KA only) down-regulation of γ2 mRNA and lasting decreases in subunit α5, β3, and δ mRNAs that were prominent in all hippocampal and parahippocampal areas. ⋯ Their decrease could be related to decreased tonic inhibition or may merely reflect compensatory changes. In contrast, expression of subunit α4 that may also mediate tonic inhibition when associated with the δ-subunit was significantly upregulated in the DG and in the proximal subiculum at late intervals. Thus, concomitant up-regulation of subunit γ2, α1 and α4 mRNAs (and loss in δ-subunits) ultimately indicates significant rearrangement of GABAA receptor composition after KA-induced seizures.
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Front Neural Circuit · Jan 2013
Effect of phase response curve skew on synchronization with and without conduction delays.
A central problem in cortical processing including sensory binding and attentional gating is how neurons can synchronize their responses with zero or near-zero time lag. For a spontaneously firing neuron, an input from another neuron can delay or advance the next spike by different amounts depending upon the timing of the input relative to the previous spike. This information constitutes the phase response curve (PRC). ⋯ However, for right skew there is a preferred antiphase mode at short delays. In contrast to mutual excitation, left skew destabilizes antiphase for mutual inhibition so that synchrony dominates at short delays as well. These pairwise synchronization tendencies constrain the synchronization properties of neurons embedded in larger networks.
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Front Neural Circuit · Jan 2013
Neural activity in mediodorsal nucleus of thalamus in rats performing a working memory task.
The neural circuit consisting of mediodorsal nucleus (MDN) of thalamus and prefrontal cortex (PFC) has been implicated in working memory. In order to investigate whether and how the rodent MDN processes working memory-related signals, we recorded activity of single neurons from the MDN in rats performing a delayed spatial alternation task. ⋯ These results are in contrast to the finding in monkeys that both MDN and PFC persistently maintain task-related neural signals throughout delay period. Our results do not support sustained MDN-PFC interactions as a general mechanism for mediating working memory across different behavioral tasks and/or animal species.
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Front Neural Circuit · Jan 2013
Reciprocal connectivity between mitral cells and external plexiform layer interneurons in the mouse olfactory bulb.
Proper brain function relies on exquisite balance between excitation and inhibition, where inhibitory circuits play fundamental roles toward sculpting principle neuron output and information processing. In prominent models of olfactory bulb circuitry, inhibition of mitral cells by local interneurons sharpens odor tuning and provides contrast enhancement. Mitral cell inhibition occurs at both mitral cell apical dendrites and deep-layer dendrodendritic synapses between granule cells, the most abundant population of inhibitory interneurons in the olfactory bulb. ⋯ Here, we report a novel circuitry with strong and reciprocal connectivity between a subpopulation of previously uncharacterized Corticotropin-Releasing Hormone (CRH)-expressing interneurons located in the external plexiform layer (EPL), and mitral cells. Using cell type-specific genetic manipulations, imaging, optogenetic stimulation, and electrophysiological recordings, we reveal that CRH-expressing EPL interneurons strongly inhibit mitral cell firing, and that they are reciprocally excited by fast glutamatergic mitral cell input. These findings functionally identify a novel subpopulation of olfactory bulb interneurons that show reciprocal connectivity with mitral cells, uncovering a previously unknown, and potentially critical player in olfactory bulb circuitry that may influence lateral interactions and/or facilitate odor processing.
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Front Neural Circuit · Jan 2013
Acutely increasing δGABA(A) receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus.
Extrasynaptic γ-aminobutyric acid type A (GABA(A)) receptors that contain the δ subunit (δGABA(A) receptors) are expressed in several brain regions including the dentate gyrus (DG) and CA1 subfields of the hippocampus. Drugs that increase δGABA(A) receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABA(A) receptor-preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) enhances discrimination memory and increases neurogenesis in the DG. ⋯ Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd(-/-) mice, an effect that was blocked by GABA(A) receptor antagonist bicuculline. Thus, acutely increasing δGABA(A) receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABA(A) receptor activity.