Saporin, which is extracted from Saponaria officinalis, is a protein toxin that inactivates ribosomes. Saporin itself is non-selective toxin but acquires high specificity after conjugation with different ligands such as signaling peptides or antibodies to some surface proteins expressed in a chosen cell subpopulation. The saporin-based conjugated toxins were widely adopted in neuroscience as a convenient tool to induce highly selective degeneration of desired cell subpopulation. Induction of selective cell death is one of approaches used to model neurodegenerative diseases, study functions of certain cell subpopulations in the brain, and therapy. Here, we review studies where saporin-based conjugates were used to analyze cell mechanisms of sleep, general anesthesia, epilepsy, pain, and development of Parkinson’s and Alzheimer’s diseases. Limitations and future perspectives of use of saporin-based toxins in neuroscience are discussed.

In this study we quantified maternal behavior in genetic epileptic rats with deficiencies in the DA system known to be involved in maternal behavior in order to assess whether these rats have disturbances in maternal care. Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a genetic model for generalized absence epilepsy and Wistar rats were compared. Maternal behavior parameters and activity scores were quantified from post-natal day (PND) 4-6 in an open field in the presence of pups. WAG/Rij rats had less approaches to the pups and higher latencies of approaching them compared to Wistar, while locomotion showed a different pattern over days. This confirms the hypothesis that animals with absence epilepsy show more poor maternal behavior and that these effects cannot be solely attributed to differences in locomotor activity. It is proposed that the reduction in maternal care is attributed to low activity in the mesolimbic DA system.

Haloperidol treatment during pre- and post-natal period affects maternal behavior and this may have long-term effects on the offspring. We examined whether early haloperidol administration to Wistar-Albino-Glaxo dams from Rijswijk (WAG/Rij) and in Wistar control rats would affect maternal care and as a consequence, seizure susceptibility and behavior in the WAG/Rij?s offspring at 3-4 months of age. Nursing dams of this well-validated genetic animal model of absence epilepsy and control dams were injected with haloperidol or saline at PPD 1 to 6. Maternal behavior was evaluated at PPD 7 to 9. Haloperidol-injected WAG/Rij dams showed more pup carryings compared with saline-injected mothers, this effect was not noticed in control Wistar dams. The offspring of haloperidol-treated WAG/Rij dams, tested during adulthood, showed heightened behavioral activity (time spent into the open arms, head dips) in the elevated plus-maze, as well as shorter spikewave discharges (SWD) as measured in their electroencephalographic activity compared with saline-treated rats. Overall, it can be concluded that deviancies in the DA system as induced by haloperidol facilitates pup carrying/retrieval behavior in WAG/Rij rats and reduces seizure activity of the offspring in adulthood. Therefore, inter-individual differences in seizure properties and behavior in genetically predisposed animals may be due to differences in maternal behavior of the dams.

We performed RNA sequencing of the dorsal and ventral parts of the hippocampus and compared it with previously published data to determine the differences in the dorsoventral gradients of gene expression that may result from biological or technical variability. Our data suggest that the dorsal and ventral parts of the hippocampus differ in the expression of genes related to signaling pathways mediated by classical neurotransmitters (glutamate, GABA, monoamines, etc.) as well as peptide and Wnt ligands. These hippocampal parts also diverge in the expression of axon-guiding molecules (both receptors and ligands) and splice isoforms of genes associated with intercellular signaling and cell adhesion. Furthermore, analysis of differential expressions of genes specific for astrocytes, microglia, oligodendrocytes, and vascular cells suggests that non-neuronal cells may also differ in the characteristics between hippocampal parts. Analysis of expression of transposable elements showed that depletion of ribosomal RNA strongly increased the representation of transposable elements in the RNA libraries and helped to detect a weak predominance of expression of these elements in the ventral hippocampus. Our data revealed new molecular dimensions of functional differences between the dorsal and ventral hippocampus and points to possible cascades that may be involved in the longitudinal organization of the hippocampus.

Cholinergic septohippocampal projections originating from the medial septal area (MSA) play a critical role in regulating attention, memory formation, stress responses, and synaptic plasticity. Cholinergic axons from the MSA extensively innervate all hippocampal regions, providing a structural basis for the simultaneous release of acetylcholine (ACh) across the entire hippocampus. However, this widespread release appears inconsistent with the specific functional roles that ACh is thought to serve during distinct behaviors. A key unresolved question is how the dynamics of ACh tissue concentrations determine its ability to activate different receptor types and coordinate individual synaptic pathways. Here, we highlight several debated issues, including the potential intrinsic source of ACh within the hippocampus – such as cholinergic interneurons – and the co-release of ACh with GABA. Furthermore, we discuss recent findings on in vivo ACh concentration dynamics, which present a new dilemma for understanding ACh signaling in the hippocampus: the contrast between “global” ACh release, driven by synchronous activation of MSA neurons, and “local” release, which may be influenced by yet unidentified factors.