Abstract
The neurological impairments associated with traumatic brain injury include learning and memory deficits and increased risk of seizures. The hippocampus is critically involved in both of these phenomena and highly susceptible to damage by traumatic brain injury. To examine network activity in the hippocampal CA1 region after lateral fluid percussion injury, we used a combination of voltage-sensitive dye, field potential, and patch clamp recording in mouse hippocampal brain slices. When the stratum radiatum (SR) was stimulated in slices from injured mice, we found decreased depolarization in SR and increased hyperpolarization in stratum oriens (SO), together with a decrease in the percentage of pyramidal neurons firing stimulus-evoked action potentials. Increased hyperpolarization in SO persisted when glutamatergic transmission was blocked. However, we found no changes in SO responses when the alveus was stimulated to directly activate SO. These results suggest that the increased SO hyperpolarization evoked by SR stimulation was mediated by interneurons that have cell bodies and/or axons in SR, and form synapses in stratum pyramidale and SO. A low concentration (100 nM) of the synthetic cannabinoid WIN55,212-2, restored CA1 output in slices from injured animals. These findings support the hypothesis that increased GABAergic signaling by cannabinoid-sensitive interneurons contributes to the reduced CA1 output following traumatic brain injury.
Highlights
A full understanding of the macrocircuits that underlie brain function and behavior requires a complete understanding of the microcircuits upon which they are built
stratum radiatum (SR) STIMULATION Previous reports demonstrated a decrease in SR-evoked and recorded CA1 field potentials 6–8 days post-injury (Witgen et al, 2005; Norris and Scheff, 2009; Cole et al, 2010), so we began by evaluating CA1 SR, stratum pyramidale (SP), and stratum oriens (SO) Voltage-sensitive dye (VSD) signals in response to SR stimulation to determine if VSD signals showed a similar post-injury decrease in SR-evoked responses
Our results are consistent with these reports, yet provide layer-specific information regarding these changes and identify a specific population of cells altered by injury
Summary
A full understanding of the macrocircuits that underlie brain function and behavior requires a complete understanding of the microcircuits upon which they are built. Network excitability increases in the dentate gyrus, but decreases in CA1. Afferents from the granule cells in the DG project to pyramidal neurons in the CA3 region, which in turn project to pyramidal neurons in CA1. The afferents from those CA3 pyramidal neurons are known as the Schaffer Collateral pathway (Figures 1A,B). Another feature of hippocampal anatomy is its laminar organization. The stratum radiatum (SR) contains the proximal portion of the CA1 pyramidal neuron apical dendrites as well as the Schaffer collaterals, which form synapses on those apical dendrites. The basal dendrites of the CA1 pyramidal neurons extend into the stratum oriens (SO), which contains the CA1 pyramidal neuron axons, which radiate outward and enter the alveus
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