Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration.

Despite the recent emergence of multiple cellular and molecular strategies to restore vision in retinal disorders, it remains unclear to what extent central visual circuits can recover when retinal defects are corrected in adulthood. We addressed this question in an Lrat mouse model of Leber congenital amaurosis (LCA) in which retinal light sensitivity and optomotor responses are partially restored by 9-cis-retinyl acetate administration in adulthood. Following treatment, two-photon calcium imaging revealed increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1).

Juvenile depletion of microglia reduces orientation but not high spatial frequency selectivity in mouse V1.

Microglia contain multiple mechanisms that shape the synaptic landscape during postnatal development. Whether the synaptic changes mediated by microglia reflect the developmental refinement of neuronal responses in sensory cortices, however, remains poorly understood. In postnatal life, the development of increased orientation and spatial frequency selectivity of neuronal responses in primary visual cortex (V1) supports the emergence of high visual acuity.

Functional Differentiation of Mouse Visual Cortical Areas Depends upon Early Binocular Experience.

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons.

Long-term Monocular Deprivation during Juvenile Critical Period Disrupts Binocular Integration in Mouse Visual Thalamus.

Study of the neural deficits caused by mismatched binocular vision in early childhood has predominantly focused on circuits in the primary visual cortex (V1). Recent evidence has revealed that neurons in mouse dorsolateral geniculate nucleus (dLGN) can undergo rapid ocular dominance plasticity following monocular deprivation (MD). It remains unclear, however, whether the long-lasting deficits attributed to MD during the critical period originate in the thalamus.

Feature-Specific Organization of Feedback Pathways in Mouse Visual Cortex.

Higher and lower cortical areas in the visual hierarchy are reciprocally connected [1]. Although much is known about how feedforward pathways shape receptive field properties of visual neurons, relatively little is known about the role of feedback pathways in visual processing. Feedback pathways are thought to carry top-down signals, including information about context (e.

Excitatory Inputs Determine Phase-Locking Strength and Spike-Timing of CA1 Stratum Oriens/Alveus Parvalbumin and Somatostatin Interneurons during Intrinsically Generated Hippocampal Theta Rhythm.

Unlabelled: Theta oscillations are essential for learning and memory, and their generation requires GABAergic interneurons. To better understand how theta is generated, we explored how parvalbumin (PV) and somatostatin (SOM) interneurons in CA1 stratum oriens/alveus fire during hippocampal theta and investigated synaptic mechanisms underlying their behavior. Combining the use of transgenic mice to visually identify PV and SOM interneurons and the intact hippocampal preparation that can generate theta oscillations in vitro without cholinergic agonists, we performed simultaneous field and whole-cell recordings.

Network models provide insights into how oriens-lacunosum-moleculare and bistratified cell interactions influence the power of local hippocampal CA1 theta oscillations.

Hippocampal theta is a 4-12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those between oriens-lacunosum-moleculare (OLM) interneurons and bistratified cells (BiCs), make their contribution to network rhythms difficult to determine experimentally. We created network models that are tied to experimental work at both cellular and network levels to explore how these interneuron interactions affect the power of local oscillations.

Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency.

Hippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic connections and oscillates spontaneously at theta frequencies.

Simple, biologically-constrained CA1 pyramidal cell models using an intact, whole hippocampus context.

The hippocampus is a heavily studied brain structure due to its involvement in learning and memory. Detailed models of excitatory, pyramidal cells in hippocampus have been developed using a range of experimental data. These models have been used to help us understand, for example, the effects of synaptic integration and voltage gated channel densities and distributions on cellular responses.

Experimentally constrained CA1 fast-firing parvalbumin-positive interneuron network models exhibit sharp transitions into coherent high frequency rhythms.

The coupling of high frequency oscillations (HFOs; >100 Hz) and theta oscillations (3-12 Hz) in the CA1 region of rats increases during REM sleep, indicating that it may play a role in memory processing. However, it is unclear whether the CA1 region itself is capable of providing major contributions to the generation of HFOs, or if they are strictly driven through input projections. Parvalbumin-positive (PV+) interneurons may play an essential role in these oscillations due to their extensive connections with neighboring pyramidal cells, and their characteristic fast-spiking.

Glutamatergic neurons of the mouse medial septum and diagonal band of Broca synaptically drive hippocampal pyramidal cells: relevance for hippocampal theta rhythm.

Neurons of the medial septum and diagonal band of Broca (MS-DBB) provide an important input to the hippocampus and are critically involved in learning and memory. Although cholinergic and GABAergic MS-DBB neurons are known to modulate hippocampal activity, the role of recently described glutamatergic MS-DBB neurons is unknown. Here, we examined the electrophysiological properties of glutamatergic MS-DBB neurons and tested whether they provide a functional synaptic input to the hippocampus.

Chronic exposure to nerve growth factor increases acetylcholine and glutamate release from cholinergic neurons of the rat medial septum and diagonal band of Broca via mechanisms mediated by p75NTR.

Basal forebrain neurons play an important role in memory and attention. In addition to cholinergic and GABAergic neurons, glutamatergic neurons and neurons that can corelease acetylcholine and glutamate have recently been described in the basal forebrain. Although it is well known that nerve growth factor (NGF) promotes synaptic function of cholinergic basal forebrain neurons, how NGF affects the newly identified basal forebrain neurons remains undetermined.