The neural basis for a persistent internal state in Drosophila females.

Sustained changes in mood or action require persistent changes in neural activity, but it has been difficult to identify the neural circuit mechanisms that underlie persistent activity and contribute to long-lasting changes in behavior. Here, we show that a subset of Doublesex+ pC1 neurons in the Drosophila female brain, called pC1d/e, can drive minutes-long changes in female behavior in the presence of males. Using automated reconstruction of a volume electron microscopic (EM) image of the female brain, we map all inputs and outputs to both pC1d and pC1e. This reveals strong recurrent connectivity between, in particular, pC1d/e neurons and a specific subset of Fruitless+ neurons called aIPg. We additionally find that pC1d/e activation drives long-lasting persistent neural activity in brain areas and cells overlapping with the pC1d/e neural network, including both Doublesex+ and Fruitless+ neurons. Our work thus links minutes-long persistent changes in behavior with persistent neural activity and recurrent circuit architecture in the female brain.

Long-term mental states such as arousal and mood variations rely on persistent changes in the activity of certain neural circuits which have been difficult to identify. For instance, in male fruit flies, the activation of a particular circuit containing 'P1 neurons' can escalate aggressive and mating behaviors. However, less is known about the neural networks that underlie arousal in female flies. A group of female-specific, 'pC1 neurons' similar to P1 neurons could play this role, but it was unclear whether it could drive lasting changes in female fly behavior. To investigate this question, Deutsch et al. stimulated or shut down pC1 circuits in female flies, and then recorded the insects' interactions with male flies. Stimulation was accomplished using optogenetics, a technique which allows researchers to precisely control the activity of specially modified light-sensitive neurons. Silencing pC1 neurons in female flies diminished their interest in male partners and their suitor's courtship songs. Activating these neural circuits made the females more receptive to males; it also triggered long-lasting aggressive behaviors not typically observed in virgin females, such as shoving and chasing. Deutsch et al. then identified the brain cells that pC1 neurons connect to, discovering that these neurons are part of an interconnected circuit also formed of aIPg neurons ­ a population of fly brain cells that shows sex differences and is linked to female aggression. The brains of females were then imaged as pC1 neurons were switched on, revealing a persistent activity which outlasted the activation in circuits containing both pC1 and aIPg neurons. Thus, these results link neural circuit architecture to long lasting changes in neural activity, and ultimately, in behavior. Future experiments can build on these results to determine how this circuit is activated during natural social interactions.

Connecting Neural Codes with Behavior in the Auditory System of Drosophila.

Brains are optimized for processing ethologically relevant sensory signals. However, few studies have characterized the neural coding mechanisms that underlie the transformation from natural sensory information to behavior. Here, we focus on acoustic communication in Drosophila melanogaster and use computational modeling to link natural courtship song, neuronal codes, and female behavioral responses to song. We show that melanogaster females are sensitive to long timescale song structure (on the order of tens of seconds). From intracellular recordings, we generate models that recapitulate neural responses to acoustic stimuli. We link these neural codes with female behavior by generating model neural responses to natural courtship song. Using a simple decoder, we predict female behavioral responses to the same song stimuli with high accuracy. Our modeling approach reveals how long timescale song features are represented by the Drosophila brain and how neural representations can be decoded to generate behavioral selectivity for acoustic communication signals.

Inhibitory connections in the honeybee antennal lobe are spatially patchy.

The olfactory system is a classical model for studying sensory processing. The first olfactory brain center [the olfactory bulb of vertebrates and the antennal lobe (AL) of insects] contains spherical neuropiles called glomeruli. Each glomerulus receives the information from one olfactory receptor type. Interglomerular computation is accomplished by lateral connectivity via interneurons. However, the spatial and functional organization of these lateral connections is not completely understood. Here we studied the spatial logic in the AL of the honeybee. We combined topical application of neurotransmitters, olfactory stimulations, and in vivo calcium imaging to visualize the arrangement of lateral connections. Suppression of activity in a single glomerulus with γ-aminobutyric acid (GABA) while presenting an odor reveals the existence of inhibitory interactions. Stimulating a glomerulus with acetylcholine (ACh) activates inhibitory interglomerular connections that can reduce odor-evoked responses. We show that this lateral network is patchy, in that individual glomeruli inhibit other glomeruli with graded strength, but in a spatially discontinuous manner. These results suggest that processing of olfactory information requires combinatorial activity patterns with complex topologies across the AL.

Embedding of cortical representations by the superficial patch system.

Pyramidal cells in layers 2 and 3 of the neocortex of many species collectively form a clustered system of lateral axonal projections (the superficial patch system--Lund JS, Angelucci A, Bressloff PC. 2003. Anatomical substrates for functional columns in macaque monkey primary visual cortex. Cereb Cortex. 13:15-24. or daisy architecture--Douglas RJ, Martin KAC. 2004. Neuronal circuits of the neocortex. Annu Rev Neurosci. 27:419-451.), but the function performed by this general feature of the cortical architecture remains obscure. By comparing the spatial configuration of labeled patches with the configuration of responses to drifting grating stimuli, we found the spatial organizations both of the patch system and of the cortical response to be highly conserved between cat and monkey primary visual cortex. More importantly, the configuration of the superficial patch system is directly reflected in the arrangement of function across monkey primary visual cortex. Our results indicate a close relationship between the structure of the superficial patch system and cortical responses encoding a single value across the surface of visual cortex (self-consistent states). This relationship is consistent with the spontaneous emergence of orientation response-like activity patterns during ongoing cortical activity (Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A. 2003. Spontaneously emerging cortical representations of visual attributes. Nature. 425:954-956.). We conclude that the superficial patch system is the physical encoding of self-consistent cortical states, and that a set of concurrently labeled patches participate in a network of mutually consistent representations of cortical input.

High-amplitude positive spikes recorded extracellularly in cat visual cortex.

We simulated the shape and amplitude of extracellular action potentials (APs or "spikes") using biophysical models based on detailed reconstructions of single neurons from the cat's visual cortex. We compared these predictions with spikes recorded from the cat's primary visual cortex under a standard protocol. The experimental data were derived from a large number of neurons throughout all layers. The majority of spikes were biphasic, with a dominant negative peak (mean amplitude, -0.11 mV), whereas a minority of APs had a dominant positive peak of +0.54-mV mean amplitude, with a maximum of +1.5 mV. The largest positive amplitude spikes were recorded in layer 5. The simulations demonstrated that a pyramidal neuron under known biophysical conditions may generate a negative peak with amplitude up to -1.5 mV, but that the amplitude of the positive peak may be at most 0.5 mV. We confirmed that spikes with large positive peaks were not produced by juxtacellular patch recordings. We conclude that there is a significant gap in our present understanding of either the spike-generation process in pyramidal neurons, the biophysics of extracellular recording, or both.

Inactivation of lateral connections in cat area 17.

Excitatory synapses arising from local neurons in the cat visual cortex are much more numerous than the thalamocortical synapses, which provide the primary sensory input. Many of these local circuit synapses are involved in the connections between cortical layers, but lateral connections within layers provide a major component of the local circuit synapses. We tested the influence of these lateral connections in the primary visual cortex of cats by inactivating small patches of cortex about 450 microm lateral from the recording pipette. By use of the neurotransmitter gamma-aminobutyric acid (GABA), small patches of cortex were inhibited and released from inhibition in seconds. Orientation tuning curves derived from responses to oriented drifting gratings were obtained during short control periods interleaved with periods of GABA inactivation. About 30% of the cells (18/62, recorded in all layers) changed their orientation tuning when a small portion of their lateral input was silenced. There was no broadening of the orientation tuning curve during lateral inactivation. Instead, the recorded cells shifted their preferred orientation towards the orientation of the inactivated site. One explanation is that the GABA inactivation alters the balance of excitatory and inhibitory inputs to a cell, which results in a shift of the cell's preferred orientation.

The effect of moving textures on the responses of cells in the cat's dorsal lateral geniculate nucleus.

Neurons in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized cat were activated with test stimuli (flashing spots, counterphased gratings and moving bars) in the presence of a moving background texture. Moving texture alone produced mild excitation, as a result of stimulation of the receptive field centre. Fast moving coarse textures were more effective than fine slow moving textures. The predominant effect of texture motion, however, was to reduce the response to all test stimuli displayed in the receptive field centre. The effects were similar for X- and Y-like cells. In the case of flashed spots, the sustained response was more strongly suppressed than the transient response. The direction of motion of the texture and differences in the relative motion of bar and texture had no influence on the degree of suppression. These observations are similar to effects seen on cat retinal ganglion cells, and are probably a form of gain control. Such suppressive effects are transmitted to the cortex and are likely to be evoked by large gratings, textures and by natural stimuli, all of which activate extensive regions of the receptive field surround.