Извилистость пути путь на вершину горы извилист, независимо от того, улитка ты

улитка ты или великан – говорила мудрая улитка, ползущая на

вершину Фудзиямы

The way to the top
of the mountain is not straight, and it does not depend on whether you are the snail or a giant – said the snail moving to the top of Fudziyama

ТИХО. ТИХО ПОЛЗИ, УЛИТКА
ВВЕРХ ПО СКЛОНУ ФУДЗИ
ВВЕРХ ДО САМЫХ ВЫСОТ
Slowly, slowly crawl, the snail
Up the Fudzi slope
Up to the very top

and Neurophysiology,
Russian Academy of Sciences

1012 neurons establish 1015 specific synaptic connections to produce our

functional thinking brain

“critical periods”

réseaux
IV
0 synapse
10 15 synapses
III
Formation de synapses
Environmental
Genetic
Insults
Des unités

fonctionnelles

Genes

Environment

синапсах?

Axon Is a Presynaptic Zone
Potentially Affected by Learning-Induced Nonsynaptic Plasticity
The

proposed mechanism of ‘‘remotecontrolled’’ increase in synaptic efficacy after classical conditioning in Lymnaea. In naive animals, application of amyl acetate (used as the conditioned stimulus [CS] during training) leads to a small increase in the tonic firing rate of the cerebral giant cell (CGC, cartoon trace on top). Spikes evoked by the CS in putative chemosensory neurons (SN) of the lip only evoke small excitatory postsynaptic potentials in the command-like cerebral-to-buccal interneurons (CBI) of the feeding system. In conditioned
animals, the CGC soma and proximal axonal segments are persistently depolarized

Nikitin, Balaban, Kemenes, Current Biology, 2013

Calcium Transients and Spikes in the Cerebral Side Branch of
the

CGC
(A) The inactivation curve of the potassium A current (IA) of the CGC Inset: CGC MP values (mean 6 SEM) from preparations from control (blue lines) and trained animals (red lines) plotted on the relevant section of the inactivation curve. (Bi) Comparison of the ratios of the calcium signal amplitudes measured at the most proximal (1) and most distal (3) regions of interest (ROIs; see bottom panel) in a preparation from a naïve control animal before and after 4-AP treatment.Dashed lines indicate baseline levels and the peak of the calcium transient in ROI 1, respectively. Solid line indicates the peak of the calcium transient in ROI3. The electrophysiologically recorded soma spikes that triggered the axonal calcium transients (recorded with Oregon green) are also shown.
(Bii) The ratio (mean 6 SEM values from eight preparations) is significantly higher after the
application of 4-AP (p < 0.05).
(C) Attenuation of spikes in the cerebral side branch of the CGC and its reduction by 4-AP recorded with the voltage-sensitive dye JPW1114..

PRESYNAPTIC NEURON
NEURITES OF POSTSYNAPTIC NEURONS

(PKC)

Functions in the storage of memory.

торжественно объявила, что ученые из Медицинского центра в Бруклине под

руководством доктора Сактора открыли «молекулу памяти», воздействуя на которую можно будет вскоре стирать в мозгу человека любое нежелательное ему воспоминание, тем самым облегчая ему всю последующую жизнь.
Фермент протеинкиназа М-зета считается одним из ключевых элементов механизма долговременной памяти (это было установлено несколько лет назад), однако более всего он — если верить авторам — интересен тем, что с его помощью сохраняются только комплексные воспоминания, детальная информация о совершенных действиях и пережитых потрясениях. Следовательно, при выборочном уничтожении молекул протеинкиназы М-зета человек может «забыть» о неугодных ему событиях и переживаниях, причем функционирование его мозга не нарушится.

insular cortex. (A) ZIP/vehicle were
administered 3 mo after training, and

memory was tested 2 d later. The dashed line indicates equal
preference for the CS and water, i.e., AI = 50. (B) ZIP/vehicle/scrambled ZIP were administered 1 mo
after training, and memory was tested 12 d later. Saccharin was the CS in both A and B.

gene has two promoters, one producing a full-length protein kinase

Cζ (PKCζ) from exons encoding a regulatory domain (Reg; shown in red) and a catalytic domain (Cat; shown in green). In neurons, an internal promoter produces a protein kinase Mζ (PKMζ) mRNA that encodes a ζ catalytic domain without a regulatory domain. The PKMζ mRNA is transported to dendrites and is translationally repressed by PIN1 (protein interacting with NIMA1). During long-term potentiation induction, multiple signalling pathways stimulated by NMDAR activation are required to release the translational block. Once synthesized, PKMζ binds to and is phosphorylated by phosphoinositide-dependent protein kinase 1 (PDK1), which increases the constitutive kinase activity of PKMζ. PKMζ then initiates a positive feedback loop through inhibition of PIN1 to maintain increased dendritic translation of the PKMζ message. PKMζ potentiates AMPAR responses by increasing the number of the receptors in the postsynaptic density through the action of the trafficking protein N-ethylmaleimide-sensitive factor (NsF).
CaMKII, Ca2+/calmodulin-dependent protein kinase II; glu, glutamate; MAPK, mitogen-activated protein kinase; mToR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; PKA, protein kinase A

initial acqusition of a memory during which the long-term memory

is thought to be forming and stabilizing. Reconsolidation – even more hypothetical process that suggests a possibility for long-term memory to re-enter a consolidation phase when reactivated

testing for context conditioning, no reminding. B - averaged amplitudes

(+SEM) of withdrawal responses in three groups of snails measured in two different contexts.

Learning & Memory, 2005

immediately after reminding. B - averaged amplitudes (±SEM) of withdrawal

responses in three groups of snails measured in two different contexts.



MEMORY IS ERASED???

synthase (NOS) — or higher nitrogen oxides (represented by NOx)

can react, in the presence of electron acceptors, with protein thiols to generate S-nitrosylated proteins (SNO proteins). In addition, nitrosylation can occur through transnitrosylation involving a nitrosothiol (SNO), such as S-nitrosoglutathione (GSNO), and an acceptor thiol.

group is post-translationally added to a protein.
S-nitrosylation, discovered by Joseph

Loscalzo, is an important biological reaction of nitric oxide; it refers to the conversion of thiol groups, including cysteine residues in proteins, to form S-nitrosothiols (RSNOs). S-Nitrosylation is a mechanism for dynamic, post-translational regulation of most or all major classes of protein.

activates protein synthesis via G-pathways, while in big concentrations LOCALLY

impairs proteins functioning via S-nitrosylation mechanism.
Question:
? NO is necessary both for memory formation and local memory plastification in synapses?

feeding in FC context