In Vivo Femtosecond Laser Subsurface Cortical Microtransections Attenuate Acute Rat Focal Seizures.

Recent evidence shows that seizures propagate primarily through supragranular cortical layers. To selectively modify these circuits, we developed a new technique using tightly focused, femtosecond infrared laser pulses to make as small as ~100 µm-wide subsurface cortical incisions surrounding an epileptic focus. We use this "laser scalpel" to produce subsurface cortical incisions selectively to supragranular layers surrounding an epileptic focus in an acute rodent seizure model. Compared with sham animals, these microtransections completely blocked seizure initiation and propagation in 1/3 of all animals. In the remaining animals, seizure frequency was reduced by 2/3 and seizure propagation reduced by 1/3. In those seizures that still propagated, it was delayed and reduced in amplitude. When the recording electrode was inside the partially isolated cube and the seizure focus was on the outside, the results were even more striking. In spite of these microtransections, somatosensory responses to tail stimulation were maintained but with reduced amplitude. Our data show that just a single enclosing wall of laser cuts limited to supragranular layers led to a significant reduction in seizure initiation and propagation with preserved cortical function. Modification of this concept may be a useful treatment for human epilepsy.

Unique functional responses differentially map onto genetic subtypes of dopamine neurons.

Dopamine neurons are characterized by their response to unexpected rewards, but they also fire during movement and aversive stimuli. Dopamine neuron diversity has been observed based on molecular expression profiles; however, whether different functions map onto such genetic subtypes remains unclear. In this study, we established that three genetic dopamine neuron subtypes within the substantia nigra pars compacta, characterized by the expression of Slc17a6 (Vglut2), Calb1 and Anxa1, each have a unique set of responses to rewards, aversive stimuli and accelerations and decelerations, and these signaling patterns are highly correlated between somas and axons within subtypes. Remarkably, reward responses were almost entirely absent in the Anxa1+ subtype, which instead displayed acceleration-correlated signaling. Our findings establish a connection between functional and genetic dopamine neuron subtypes and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions.

Parallel processing by distinct classes of principal neurons in the olfactory cortex.

Understanding how distinct neuron types in a neural circuit process and propagate information is essential for understanding what the circuit does and how it does it. The olfactory (piriform, PCx) cortex contains two main types of principal neurons, semilunar (SL) and superficial pyramidal (PYR) cells. SLs and PYRs have distinct morphologies, local connectivity, biophysical properties, and downstream projection targets. Odor processing in PCx is thought to occur in two sequential stages. First, SLs receive and integrate olfactory bulb input and then PYRs receive, transform, and transmit SL input. To test this model, we recorded from populations of optogenetically identified SLs and PYRs in awake, head-fixed mice. Notably, silencing SLs did not alter PYR odor responses, and SLs and PYRs exhibited differences in odor tuning properties and response discriminability that were consistent with their distinct embeddings within a sensory-associative cortex. Our results therefore suggest that SLs and PYRs form parallel channels for differentially processing odor information in and through PCx.

Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation.

It is well established that seizures beget seizures, yet the cellular processes that underlie progressive epileptogenesis remain unclear. Here, we use optogenetics to briefly activate targeted populations of mouse piriform cortex (PCx) principal neurons in vivo. After just 3 or 4 days of stimulation, previously subconvulsive stimuli trigger massive, generalized seizures. Highly recurrent allocortices are especially prone to "optokindling." Optokindling upsets the balance of recurrent excitation and feedback inhibition. To understand how this balance is disrupted, we then selectively reactivate the same neurons in vitro. Surprisingly, we find no evidence of heterosynaptic potentiation; instead, we observe a marked, pathway-specific decrease in feedback inhibition. We find no loss of inhibitory interneurons; rather, decreased GABA synthesis in feedback inhibitory neurons appears to underlie weakened inhibition. Optokindling will allow precise identification of the molecular processes by which brain activity patterns can progressively and pathologically disrupt the balance of cortical excitation and inhibition.

Recurrent circuitry is required to stabilize piriform cortex odor representations across brain states.

Pattern completion, or the ability to retrieve stable neural activity patterns from noisy or partial cues, is a fundamental feature of memory. Theoretical studies indicate that recurrently connected auto-associative or discrete attractor networks can perform this process. Although pattern completion and attractor dynamics have been observed in various recurrent neural circuits, the role recurrent circuitry plays in implementing these processes remains unclear. In recordings from head-fixed mice, we found that odor responses in olfactory bulb degrade under ketamine/xylazine anesthesia while responses immediately downstream, in piriform cortex, remain robust. Recurrent connections are required to stabilize cortical odor representations across states. Moreover, piriform odor representations exhibit attractor dynamics, both within and across trials, and these are also abolished when recurrent circuitry is eliminated. Here, we present converging evidence that recurrently-connected piriform populations stabilize sensory representations in response to degraded inputs, consistent with an auto-associative function for piriform cortex supported by recurrent circuitry.

Learning: Plasticity without Stabilization in Olfactory Cortex.

A new study reports unsupervised, experience-dependent reorganization, but not stabilization, of neural odor representations in the zebrafish olfactory system.