Gateways of ventral and dorsal streams in mouse visual cortex.

It is widely held that the spatial processing functions underlying rodent navigation are similar to those encoding human episodic memory (Doeller et al., 2010). Spatial and nonspatial information are provided by all senses including vision. It has been suggested that visual inputs are fed to the navigational network in cortex and hippocampus through dorsal and ventral intracortical streams (Whitlock et al., 2008), but this has not been shown directly in rodents. We have used cytoarchitectonic and chemoarchitectonic markers, topographic mapping of receptive fields, and pathway tracing to determine in mouse visual cortex whether the lateromedial field (LM) and the anterolateral field (AL), which are the principal targets of primary visual cortex (V1) (Wang and Burkhalter, 2007) specialized for processing nonspatial and spatial visual information (Gao et al., 2006), are distinct areas with diverse connections. We have found that the LM/AL border coincides with a change in type 2 muscarinic acetylcholine receptor expression in layer 4 and with the representation of the lower visual field periphery. Our quantitative analyses also show that LM strongly projects to temporal cortex as well as the lateral entorhinal cortex, which has weak spatial selectivity (Hargreaves et al., 2005). In contrast, AL has stronger connections with posterior parietal cortex, motor cortex, and the spatially selective medial entorhinal cortex (Haftig et al., 2005). These results support the notion that LM and AL are architecturally, topographically, and connectionally distinct areas of extrastriate visual cortex and that they are gateways for ventral and dorsal streams.

Parallel input channels to mouse primary visual cortex.

It is generally accepted that in mammals visual information is sent to the brain along functionally specialized parallel pathways, but whether the mouse visual system uses similar processing strategies is not known. It is important to resolve this issue because the mouse brain provides a tractable system for developing a cellular and molecular understanding of disorders affecting spatiotemporal visual processing. We have used single-unit recordings in mouse primary visual cortex to study whether individual neurons are more sensitive to one set of sensory cues than another. Our quantitative analyses show that neurons with short response latencies have low spatial acuity and high sensitivity to contrast, temporal frequency, and speed, whereas neurons with long latencies have high spatial acuity, low sensitivities to contrast, temporal frequency, and speed. These correlations suggest that neurons in mouse V1 receive inputs from a weighted combination of parallel afferent pathways with distinct spatiotemporal sensitivities.

In vivo transcranial imaging of connections in mouse visual cortex.

From the moment the mouse model took center stage for studies of cortical arealization and map formation, there was an urgent need for methods to identify areal borders in the living animal. The need was met in part by intrinsic optical signal imaging, which has been successfully applied to map topographic representations in primary visual, auditory and somatosensory cortex. However, the challenge remains to register these maps to the underlying structure. This is especially important for studies of the mouse brain in which cortical areas are often only a few hundred microns across. Here, we show that in visual cortex neuronal tracing with fluororuby and fluoroemerald can be used for transcranial imaging through the intact skull of callosal connections from the opposite side of the brain, and for mapping of topographic striate-extrastriate cortical pathways in living mice. Because callosal connections are important landmarks for cortical areas, the new method will allow registration of functional maps to underlying structures and facilitate targeted single-unit recordings in identified cortical areas.

Signaling pathways of hypocretin-1 actions on pyramidal neurons in the rat prefrontal cortex.

We have investigated the direct excitatory effects of hypocretin-1 on acutely isolated prefrontal cortical pyramidal neurons and explored the signaling mechanisms of these actions. Puff application of hypocretin-1 caused an excitation in the recorded neurons. These effects of hypocretin-1 were abolished by a phospholipase C inhibitor D609, demonstrating that phospholipase C mediates the actions of hypocretin-1. A specific protein kinase C inhibitor, bisindolylmaleimide II, blocked the excitatory actions of hypocretin-1, suggesting that protein kinase C plays a key role. Finally, protein kinase A inhibitor applied intracellularly did not affect the responses. These results indicate that hypocretin-1 excites prefrontal neurons by activation of phospholipase C and protein kinase C pathways, but not protein kinase A.

Effects of agonists and antagonists of NMDA and ACh receptors on plasticity of bat auditory system elicited by fear conditioning.

In big brown bats, tone-specific plastic changes [best frequency (BF) shifts] of cortical and collicular neurons can be evoked by auditory fear conditioning, repetitive acoustic stimuli or cortical electric stimulation. It has been shown that acetylcholine (ACh) plays an important role in evoking large long-term cortical BF shifts. However, the role of N-methyl-d-aspartate (NMDA) receptors in evoking BF shifts has not yet been studied. We found 1) NMDA applied to the auditory cortex (AC) or inferior colliculus (IC) augmented the auditory responses, as ACh did, whereas 2-amino-5-phosphovalerate (APV), an antagonist of NMDA receptors, reduced the auditory responses, as atropine did; 2) although any of these four drugs did not evoke BF shifts, they influenced the development of the long-term cortical and short-term collicular BF shifts elicited by conditioning; 3) like ACh, NMDA augmented the cortical and collicular BF shifts regardless of whether it was applied to the AC or IC; 4) endogenous ACh of the AC and IC is necessary to produce the long-term cortical and short-term collicular BF shifts; 5) blockade of collicular NMDA receptors by APV abolished the development of the collicular BF shift and made the cortical BF shift small and short-term; 6) blockade of cortical NMDA receptors by APV reduced the cortical and collicular BF shifts and made the cortical BF shift short-term; and 7) conditioning with NMDA + atropine applied to the AC evoked the small, short-term cortical BF shift, whereas conditioning with APV + ACh applied to the AC evoked the small, but long-term cortical BF shift.